Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A tumor necrosis factor receptor subtype that is expressed primarily in IMMUNE SYSTEM cells. It has specificity for membrane-bound form of TUMOR NECROSIS FACTORS and mediates intracellular-signaling through TNF RECEPTOR ASSOCIATED FACTORS.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
A tumor necrosis factor family member that is released by activated LYMPHOCYTES. Soluble lymphotoxin is specific for TUMOR NECROSIS FACTOR RECEPTOR TYPE I; TUMOR NECROSIS FACTOR RECEPTOR TYPE II; and TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 14. Lymphotoxin-alpha can form a membrane-bound heterodimer with LYMPHOTOXIN-BETA that has specificity for the LYMPHOTOXIN BETA RECEPTOR.
Established cell cultures that have the potential to propagate indefinitely.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Proteins prepared by recombinant DNA technology.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.
Antibodies produced by a single clone of cells.
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.
An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A subclass of tumor necrosis family receptors that lack cell signaling domains. They bind to specific TNF RECEPTOR LIGANDS and are believed to play a modulating role in the TNF signaling pathway. Some of the decoy receptors are products of distinct genes, while others are products of ALTERNATIVE SPLICING of the MRNA for the active receptor.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Drugs that are used to treat RHEUMATOID ARTHRITIS.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes SYNOVIAL FLUID.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Elements of limited time intervals, contributing to particular results or situations.
A cell line derived from cultured tumor cells.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Glycoproteins found on the membrane or surface of cells.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.
Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
The action of a drug in promoting or enhancing the effectiveness of another drug.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A family of inhibitory proteins which bind to the REL PROTO-ONCOGENE PROTEINS and modulate their activity. In the CYTOPLASM, I-kappa B proteins bind to the transcription factor NF-KAPPA B. Cell stimulation causes its dissociation and translocation of active NF-kappa B to the nucleus.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Substances that reduce or suppress INFLAMMATION.
A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
A signal transducing tumor necrosis factor receptor associated factor that is involved in TNF RECEPTOR feedback regulation. It is similar in structure and appears to work in conjunction with TNF RECEPTOR-ASSOCIATED FACTOR 1 to inhibit APOPTOSIS.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
A subunit of NF-kappa B that is primarily responsible for its transactivation function. It contains a C-terminal transactivation domain and an N-terminal domain with homology to PROTO-ONCOGENE PROTEINS C-REL.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
The rate dynamics in chemical or physical systems.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Intracellular signaling peptides and proteins that bind directly or indirectly to the cytoplasmic portion of TUMOR NECROSIS FACTOR RECEPTORS.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.
An encapsulated lymphatic organ through which venous blood filters.
Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.
A signal transducing tumor necrosis factor receptor associated factor that is involved in TNF RECEPTOR feedback regulation. It is similar in structure and appears to work in conjunction with TNF RECEPTOR-ASSOCIATED FACTOR 2 to inhibit APOPTOSIS.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.
An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.
ARTHRITIS that is induced in experimental animals. Immunological methods and infectious agents can be used to develop experimental arthritis models. These methods include injections of stimulators of the immune response, such as an adjuvant (ADJUVANTS, IMMUNOLOGIC) or COLLAGEN.
Transport proteins that carry specific substances in the blood or across cell membranes.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
Biologically active substances whose activities affect or play a role in the functioning of the immune system.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Adherence of cells to surfaces or to other cells.
A chemokine that is a chemoattractant for MONOCYTES and may also cause cellular activation of specific functions related to host defense. It is produced by LEUKOCYTES of both monocyte and lymphocyte lineage and by FIBROBLASTS during tissue injury. It has specificity for CCR2 RECEPTORS.
An anti-inflammatory 9-fluoro-glucocorticoid.
Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signalling and activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES.
The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Cytokine-induced cell adhesion molecule present on activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. It is important for the recruitment of leukocytes to sites of inflammation. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, p154)
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Cell adhesion molecule and CD antigen that mediates neutrophil, monocyte, and memory T-cell adhesion to cytokine-activated endothelial cells. E-selectin recognizes sialylated carbohydrate groups related to the Lewis X or Lewis A family.
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A type of inflammatory arthritis associated with PSORIASIS, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of HLA-B27-associated SPONDYLARTHROPATHY, and the absence of rheumatoid factor.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
A mixture of polymyxins B1 and B2, obtained from Bacillus polymyxa strains. They are basic polypeptides of about eight amino acids and have cationic detergent action on cell membranes. Polymyxin B is used for infections with gram-negative organisms, but may be neurotoxic and nephrotoxic.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
A tumor necrosis factor receptor subtype with specificity for TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 15. It is found in tissues containing LYMPHOCYTES and may play a role in regulating lymphocyte homeostasis and APOPTOSIS. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC
A ZINC FINGER MOTIF containing transcription factor that was originally identified as one of the IMMEDIATE-EARLY PROTEINS. It shuttles between the CYTOPLASM and the CELL NUCLEUS and is involved in destabilization of mRNAs for TUMOR NECROSIS FACTOR-ALPHA.
Neoplasm drug therapy involving an extracorporeal circuit with temporary exclusion of the tumor-bearing area from the general circulation during which high concentrations of the drug are perfused to the isolated part.
Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).
Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.
A chronic inflammatory condition affecting the axial joints, such as the SACROILIAC JOINT and other intervertebral or costovertebral joints. It occurs predominantly in young males and is characterized by pain and stiffness of joints (ANKYLOSIS) with inflammation at tendon insertions.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells.
Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M=metal) are all insoluble, except the alkali nitrites. The organic nitrites may be isomeric, but not identical with the corresponding nitro compounds. (Grant & Hackh's Chemical Dictionary, 5th ed)
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.
The parts of a macromolecule that directly participate in its specific combination with another molecule.

Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-kappaB. (1/31169)

To maintain the integrity of the vascular barrier, endothelial cells (EC) are resistant to cell death. The molecular basis of this resistance may be explained by the function of antiapoptotic genes such as bcl family members. Overexpression of Bcl-2 or Bcl-XL protects EC from tumor necrosis factor (TNF)-mediated apoptosis. In addition, Bcl-2 or Bcl-XL inhibits activation of NF-kappaB and thus upregulation of proinflammatory genes. Bcl-2-mediated inhibition of NF-kappaB in EC occurs upstream of IkappaBalpha degradation without affecting p65-mediated transactivation. Overexpression of bcl genes in EC does not affect other transcription factors. Using deletion mutants of Bcl-2, the NF-kappaB inhibitory function of Bcl-2 was mapped to bcl homology domains BH2 and BH4, whereas all BH domains were required for the antiapoptotic function. These data suggest that Bcl-2 and Bcl-XL belong to a cytoprotective response that counteracts proapoptotic and proinflammatory insults and restores the physiological anti-inflammatory phenotype to the EC. By inhibiting NF-kappaB without sensitizing the cells (as with IkappaBalpha) to TNF-mediated apoptosis, Bcl-2 and Bcl-XL are prime candidates for genetic engineering of EC in pathological conditions where EC loss and unfettered activation are undesirable.  (+info)

Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma. (2/31169)

Par-4 is a widely expressed leucine zipper protein that confers sensitization to apoptosis induced by exogenous insults. Because the expression of genes that promote apoptosis may be down-regulated during tumorigenesis, we sought to examine the expression of Par-4 in human tumors. We present here evidence that Par-4 protein levels were severely decreased in human renal cell carcinoma specimens relative to normal tubular cells. Replenishment of Par-4 protein levels in renal cell carcinoma cell lines conferred sensitivity to apoptosis. Because apoptosis may serve as a defense mechanism against malignant transformation or progression, decreased expression of Par-4 may contribute to the pathophysiology of renal cell carcinoma.  (+info)

Gene expression profiles in HTLV-I-immortalized T cells: deregulated expression of genes involved in apoptosis regulation. (3/31169)

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia, an acute and often fatal T-cell malignancy. A key step in HTLV-I-induced leukemigenesis is induction of abnormal T-cell growth and survival. Unlike antigen-stimulated T cells, which cease proliferation after a finite number of cell division, HTLV-I-infected T cells proliferate indefinitely (immortalized), thus facilitating occurrence of secondary genetic changes leading to malignant transformation. To explore the molecular basis of HTLV-I-induced abnormal T-cell survival, we compared the gene expression profiles of normal and HTLV-I-immortalized T cells using 'gene array'. These studies revealed a strikingly altered expression pattern of a large number of genes along with HTLV-I-mediated T-cell immortalization. Interestingly, many of these deregulated genes are involved in the control of programmed cell death or apoptosis. These findings indicate that disruption of the cellular apoptosis-regulatory network may play a role in the HTLV-I-mediated oncogenesis.  (+info)

Activation of IkappaB kinase beta by protein kinase C isoforms. (4/31169)

The atypical protein kinase C (PKC) isotypes (lambda/iotaPKC and zetaPKC) have been shown to be critically involved in important cell functions such as proliferation and survival. Previous studies have demonstrated that the atypical PKCs are stimulated by tumor necrosis factor alpha (TNF-alpha) and are required for the activation of NF-kappaB by this cytokine through a mechanism that most probably involves the phosphorylation of IkappaB. The inability of these PKC isotypes to directly phosphorylate IkappaB led to the hypothesis that zetaPKC may use a putative IkappaB kinase to functionally inactivate IkappaB. Recently several groups have molecularly characterized and cloned two IkappaB kinases (IKKalpha and IKKbeta) which phosphorylate the residues in the IkappaB molecule that serve to target it for ubiquitination and degradation. In this study we have addressed the possibility that different PKCs may control NF-kappaB through the activation of the IKKs. We report here that alphaPKC as well as the atypical PKCs bind to the IKKs in vitro and in vivo. In addition, overexpression of zetaPKC positively modulates IKKbeta activity but not that of IKKalpha, whereas the transfection of a zetaPKC dominant negative mutant severely impairs the activation of IKKbeta but not IKKalpha in TNF-alpha-stimulated cells. We also show that cell stimulation with phorbol 12-myristate 13-acetate activates IKKbeta, which is entirely dependent on the activity of alphaPKC but not that of the atypical isoforms. In contrast, the inhibition of alphaPKC does not affect the activation of IKKbeta by TNF-alpha. Interestingly, recombinant active zetaPKC and alphaPKC are able to stimulate in vitro the activity of IKKbeta but not that of IKKalpha. In addition, evidence is presented here that recombinant zetaPKC directly phosphorylates IKKbeta in vitro, involving Ser177 and Ser181. Collectively, these results demonstrate a critical role for the PKC isoforms in the NF-kappaB pathway at the level of IKKbeta activation and IkappaB degradation.  (+info)

Prevention of collagen-induced arthritis by gene delivery of soluble p75 tumour necrosis factor receptor. (5/31169)

Collagen type II-induced arthritis (CIA) in DBA/1 mice can be passively transferred to SCID mice with spleen B- and T-lymphocytes. In the present study, we show that infection ex vivo of splenocytes from arthritic DBA/1 mice with a retroviral vector, containing cDNA for the soluble form of human p75 receptor of tumour necrosis factor (TNF-R) before transfer, prevents the development of arthritis, bone erosion and joint inflammation in the SCID recipients. Assessment of IgG subclass levels and studies of synovial histology suggest that down-regulating the effector functions of T helper-type 1 (Th1) cells may, at least in part, explain the inhibition of arthritis in the SCID recipients. In contrast, the transfer of splenocytes infected with mouse TNF-alpha gene construct resulted in exacerbated arthritis and enhancement of IgG2a antibody levels. Intriguingly, infection of splenocytes from arthritic DBA/1 mice with a construct for mouse IL-10 had no modulating effect on the transfer of arthritis. The data suggest that manipulation of the immune system with cytokines, or cytokine inhibitors using gene transfer protocols can be an effective approach to ameliorate arthritis.  (+info)

Systemic administration of rIL-12 synergistically enhances the therapeutic effect of a TNF gene-transduced cancer vaccine. (6/31169)

Interleukin-12 (IL-12) is a potent antitumor cytokine, which induces and enhances the activity of natural killer (NK) cells, lymphokine activated killer (LAK) cells and cytotoxic T lymphocytes (CTL). IL-12 also stimulates IFN-gamma production from both T cells and NK cells. In this study, we transfected methylcholanthrene-induced fibrosarcoma (MCA-D) with TNF gene and investigated the therapeutic effect of TNF gene-transduced cancer vaccine and whether the vaccination effect is enhanced by systemic administration of recombinant IL-12 (rIL-12), in a murine model. TNF gene-transduced cancer vaccine or systemic administration of rIL-12 showed slight or moderate inhibition of pre-established tumor. However, simultaneous application of the vaccine and rIL-12 resulted in complete eradication. The cytotoxicity of CTL against parental tumor cells was enhanced with the combination of the vaccine and rIL-12, and IFN-gamma production from spleen cells also increased synergistically. Our findings show that synergistic enhancement of CTL activity and IFN-gamma production could play an important role in the antitumor effect of combination therapy using TNF gene-transduced cancer vaccine and rIL-12.  (+info)

Differential expression and translocation of protein tyrosine phosphatase 1B-related proteins in ME-180 tumor cells expressing apoptotic sensitivity and resistance to tumor necrosis factor: potential interaction with epidermal growth factor receptor. (7/31169)

Tumor necrosis factor (TNF)-induced apoptosis can be inhibited by overexpression of specific tyrosine kinases or activation of tyrosine kinase cascades, suggesting potential antagonism between apoptotic and tyrosine kinase signaling processes. In this report, the effects of TNF on EGF receptor tyrosine phosphorylation in ME-180 cell variants selected for apoptotic sensitivity (Sen) or resistance (Res) to TNF, previously shown to differentially express EGFr, were examined. Prior to the onset of apoptosis, TNF caused a significant reduction in the level of EGFr tyrosine phosphorylation in Sen cells but mediated only limited suppression of EGFr tyrosine phosphorylation in apoptotically resistant Res cells. In vitro incubation of cellular membranes with TNF derived from Sen cells stimulated a resident protein tyrosine phosphatase (PTP) activity which was able to dephosphorylate EGFr or tyrosine phosphopeptides mimicking an EGFr autophosphorylation site. In membrane preparations, PTPIB complexed with tyrosine phosphorylated EGFr and this association was disrupted by TNF through an apparent stimulation of PTP activity and turnover of phosphotyrosine. Intrinsic enzymatic activity of PTP1B was 2-3-fold higher in Sen versus Res cell lysates and a family of PTP1B-related proteins with altered C-termini was found to be highly expressed in Sen cells but absent or expressed at reduced levels in Res cells. Cytoplasmic extracts of Sen cells contained PTP1B-like proteins and TNF incubation resulted in the time dependent accumulation of PTP1B-like proteins in Sen cells but did not effect these proteins in Res cells. Together, these results suggest that specific changes in expression and subcellular distribution of phosphotyrosine modulatory proteins may play a role in conveying intrinsic apoptotic sensitivity to TNF in some tumor cell types.  (+info)

Protective effect of bactericidal/permeability-increasing protein (rBPI21) in baboon sepsis is related to its antibacterial, not antiendotoxin, properties. (8/31169)

OBJECTIVE AND SUMMARY BACKGROUND DATA: The recombinant fragment of bactericidal/permeability-increasing protein, rBPI21, has potent bactericidal activity against gram-negative bacteria as well as antiendotoxin (lipopolysaccharide [LPS]) action. On the basis of these activities, the authors sought to discover whether rBPI21 would be protective in baboons with live Escherichia coli-induced sepsis and whether the potential protective effects of rBPI21 (together with antibiotics) would be more closely related to its antibacterial or LPS-neutralizing effects. METHODS: In a prospective, randomized, placebo-controlled subchronic laboratory study, the efficacy of rBPI21 or placebo was studied over 72 hours in chronically instrumented male baboons infused with live E. coli under antibiotic therapy. RESULTS: Intravenous rBPI21 attenuated sepsis-related organ failure and increased survival significantly. Bacteremia was significantly reduced in the rBPI21 group at 2 hours after the start of the E. coli infusion, whereas circulating LPS was less affected. The in vivo formation of tumor necrosis factor was significantly suppressed by the rBPI21 treatment regimen. Microcirculation and organ function were improved. CONCLUSIONS: In baboon live E. coli sepsis, the salutary effect of rBPI21 results from a more prevalent antibacterial than antiendotoxin activity.  (+info)

The flavonoids comprise a large class of low-molecular-weight plant metabolites ubiquitously distributed in food plants. These dietary antioxidants exert significant antitumor, antiallergic, and anti-inflammatory effects. The molecular mechanisms of their biological effects remain to be clearly understood. We investigated the anti-inflammatory potentials of a safe, common dietary flavonoid component, quercetin, for its ability to modulate the production and gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) by human peripheral blood mononuclear cells (PBMC). Our results showed that quercetin significantly inhibited TNF-α production and gene expression in a dose-dependent manner. Our results provide direct evidence of the anti-inflammatory effects of quercetin by PBMC, which are mediated by the inhibition of the proinflammatory cytokine TNF-α via modulation of NF-κβ1 and Iκβ. ...
TY - JOUR. T1 - Endogenous tumor necrosis factor (TNF) production and modification of pathological lesions in experimental Escherichia coli endotoxemia of piglets. AU - Nakajima, Yasuyuki. AU - Momotani, Eiichi. AU - Takahashi, Hideyuki. AU - Ishikawa, Yoshiharu. AU - Ito, Takashi. AU - Kanesaki, Makoto. AU - Madarame, Hiroo. PY - 1995/1/1. Y1 - 1995/1/1. N2 - We examined the kinetics of tumor necrosis factor (TNF) production induced by Escherichia coli lipopolysaccharide (LPS) in relation to LPS tolerance and endotoxemic lesions of piglets. The plasma of piglets demonstrated cytotoxicity to TNF-sensitive L929 cells between 0.5 and 4 h after inoculation with 200 μg kg -1 of LPS. This cytotoxicity was neutralized by anti-bovine TNF serum. These piglets had disseminated intravascular coagulation (DIC) and meningoencephalitis. However, if piglets were first treated with three doses of 40 μg kg -1 of LPS, both TNF production and the occurrence of DIC were inhibited when 200 μg kg -1 of LPS was ...
Intravenous injection of Candida albicans into mice produced elevated serum tumor necrosis factor alpha (TNF-alpha) levels. We hypothesized that immunostimulants released in vivo from C. albicans during fungal sepsis might contribute to the elevated levels of TNF-alpha in serum. We tested this hypothesis in mice with C. albicans mannan (CAM). Increased serum TNF-alpha levels were observed following intravenous and intraperitoneal injections of CAM. Injection of CAM into mice resulted in increased serum TNF-alpha concentrations that reached 1,200 pg/ml of blood, compared with 2,400 microg/ml of blood following injection of 10 microg of endotoxin. The response to CAM was concentration dependent, requiring a minimum dose of 20 microg of CAM per g of body weight. Sera from mice were tested 30, 60, 90, and 120 min after intravenous injections with CAM. TNF-alpha concentrations were minimal 30 and 120 min after intravenous injection and maximal 60 and 90 min after CAM injection. The relative ...
Endogenous tumor necrosis factor alpha is required for enhanced antimicrobial activity against Toxoplasma gondii and Listeria monocytogenes in recombinant gamma
TY - JOUR. T1 - Antiviral effects of recombinant human tumor necrosis factor-alpha in combination with natural interferon-beta in mice infected with herpes simplex virus type 1. AU - Schmitt, David A.. AU - Sasaki, Hidetaka. AU - Pollard, Richard B.. AU - Suzuki, Fujio. PY - 1992/10/1. Y1 - 1992/10/1. N2 - The protective effects of combination therapy utilizing recombinant human TNF-alpha (rTNF-α) and natural murine interferon-beta (IFN-β) in mice infected with herpes simplex virus type 1 (HSV-1) was investigated. Mice treated with rTNF-α alone at all of the doses tested (a single i.v. administration, 2.3-2,300 μg/kg; multiple i.p. administrations 0.4-250 μg/kg) as well as mice that received IFN-β alone at doses of 16 × 104 U/kg or less resulted in a 0% survival rate. Combination therapy consisting of a single administration of rTNF- α (230 and 23 μg/kg) and multiple administrations of IFN-β (4 × 104 U/kg) resulted in a 40% and 60% survival rate. Multiple treatments of infected mice ...
TY - JOUR. T1 - Antiviral effects of recombinant human tumor necrosis factor-alpha in combination with natural interferon-beta in mice infected with herpes simplex virus type 1. AU - Schmitt, David A.. AU - Sasaki, Hidetaka. AU - Pollard, Richard B. AU - Suzuki, Fujio. PY - 1992/10/1. Y1 - 1992/10/1. N2 - The protective effects of combination therapy utilizing recombinant human TNF-alpha (rTNF-α) and natural murine interferon-beta (IFN-β) in mice infected with herpes simplex virus type 1 (HSV-1) was investigated. Mice treated with rTNF-α alone at all of the doses tested (a single i.v. administration, 2.3-2,300 μg/kg; multiple i.p. administrations 0.4-250 μg/kg) as well as mice that received IFN-β alone at doses of 16 × 104 U/kg or less resulted in a 0% survival rate. Combination therapy consisting of a single administration of rTNF- α (230 and 23 μg/kg) and multiple administrations of IFN-β (4 × 104 U/kg) resulted in a 40% and 60% survival rate. Multiple treatments of infected mice ...
TY - JOUR. T1 - Modulation of lipopolysaccharide-induced tumor necrosis factor-α and nitric oxide production by dopamine receptor agonists and antagonists in mice. AU - Haskó, G.. AU - Szabó, C.. AU - Merkel, K.. AU - Bencsics, A.. AU - Zingarelli, B.. AU - Kvetan, V.. AU - Vízi, E.. PY - 1996/3. Y1 - 1996/3. N2 - The effects of various agonists and antagonists of dopamine D1 and D2 receptors on lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production was investigated in mice. Pretreatment of animals with bromocryptine or quinpirole, agonists of dopamine D2 receptors caused a blunting of both the TNF-α and MO responses to LPS injected intraperitoneally. Sulpiride, an antagonist of dopamine D2 receptors, decreased the LPS-induced TNF-α plasma levels in a dose-dependent manner and inhibited the LPS-induced NO production by peritoneal macrophages. Bromocryptine or quinpirole blunted both the TNF-α and NO response to LPS. SCH-23390, an antagonist of ...
The human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest genes transcribed after the stimulation of a B cell through its antigen receptor or via the CD-40 pathway. In both cases, induction of TNF-alpha gene transcription can be blocked by the immunosuppressants cyclosporin A and FK506, which suggested a role for the NFAT family of proteins in the regulation of the gene in B cells. Furthermore, in T cells, two molecules of NFATp bind to the TNF-alpha promoter element kappa 3 in association with ATF-2 and Jun proteins bound to an immediately adjacent cyclic AMP response element (CRE) site. Here, using the murine B-cell lymphoma cell line A20, we show that the TNF-alpha gene is regulated in a cell-type-specific manner. In A20 B cells, the TNF-alpha gene is not regulated by NFATp bound to the kappa 3 element. Instead, ATF-2 and Jun proteins bind to the composite kappa 3/CRE site and NFATp binds to a newly identified second NFAT site centered at -76 nucleotides relative to the ...
TY - JOUR. T1 - Nutritional parameters observed during 28-day infusion of recombinant human tumor necrosis factor-α. AU - Hardin, T. C.. AU - Koeller, J. M.. AU - Kuhn, J. G.. AU - Roodman, G. D.. AU - Von Hoff, D. D.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - In conjunction with a Phase I investigation of the antineoplastic activity of recombinant human tumor necrosis factor-α (TNF-α), administered as a 28- day continuous infusion, selected nutritional parameters were evaluated to identify any effect that might be attributed to the TNF infusion. Seven clinically stable men with a variety of tumor types were studied. None had clinical or laboratory evidence of significant malnutrition before entry into the study. Five patients received 10 μg of recombinant human TNF-α per square meter per day and two patients received 25 μg/m2 per day. Indirect calorimetry assessment of resting energy expenditure, body weight, serum TNF concentration, and laboratory analysis of common nutritional markers ...
Effect of Tumor Necrosis Factor-Alpha Inhibitors on Glycemic Control in Patients with Type II Diabetes - P Deepak Udayakumar M.D.
Tumor Necrosis Factor (TNF) Inhibitor Drugs Industry Outlook 2021 The outbreak of covid-19 in the global market has made companies uncertain about their future scenario as the prolonged lock-down finds a serious economic slump. The latest survey on COVID-19 Outbreak-Global Tumor Necrosis Factor (TNF) Inhibitor Drugs Market is conducted to provide hidden gems performance analysis. Essential growth factors and study of Basis points [BPS] have been discussed in the following report. Research Report explains a detailed overview of market dynamics, segmentation, product portfolio, business plans, and the latest development in the industry.. Staying on top of market trends & drivers is crucial for decision-makers to hold this emerging opportunity. The study provides information on market trends and development, drivers, capacities, technologies, and the changing investment structure of the Tumor Necrosis Factor (TNF) Inhibitor Drugs market. The development scope, feasibility study, Tumor Necrosis ...
TY - JOUR. T1 - In vitro and in vivo inhibition of LPS-induced tumor necrosis factor-α production by dimeric gallotannin analogues. AU - Feldman, Ken S.. AU - Wilson, Sarah L.. AU - Lawlor, Michael D.. AU - Lang, Charles H.. AU - Scheuchenzuber, William J.. PY - 2002/1/1. Y1 - 2002/1/1. N2 - Designed dimeric gallotannin analogues featuring two tetragalloylglucopyranose cores connected by various hydrocarbon linkers inhibit tumor necrosis factor-α secretion from lipopolysaccharide-stimulated human peripheral blood mononuclear cells by up to 53% (5-24 μM concentration range) compared to control. Comparable suppression of tumor necrosis factor-α levels (∼50% vs control) was observed in the plasma of rats co-treated with lipopolysaccharide and specific tannin analogues selected for their lack of interleukin 1-β stimulating activity.. AB - Designed dimeric gallotannin analogues featuring two tetragalloylglucopyranose cores connected by various hydrocarbon linkers inhibit tumor necrosis ...
The combination of tumour necrosis factor-alpha-308A and interleukin-10-1082G gene polymorphisms and increased serum levels of related cytokines: susceptibility to vitiligo ...
Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, Open Access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, metabolism, cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration. The journal fills a significant void in todays scientific literature and serves as an international forum for the scientific community worldwide to translate pioneering
TY - JOUR. T1 - Murine tumour necrosis factor plays a protective role during the initial phase of the experimental infection with Trypanosoma brucei brucei. AU - MAGEZ, STEFAN. AU - LUCAS, RUDOLF. AU - DARJI, AYUB. AU - SONGA, EMMANUEL BAJYANA. AU - HAMERS, RAYMOND. AU - BAETSELIER, PATRICK DE. PY - 1993/11. Y1 - 1993/11. N2 - Soluble extracts from salivarian trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) were shown to be capable of inducing murine tumour necrosis factor (mTNF) secretion, both in vivo and in vitro, whereas the soluble extract of an intracellular trypanosome (T. cruzi) failed to do so. Furthermore, the role of mTNF during the initial phase of experimental infections with T. brucei was studied by treating infected mice with mTNF‐inducing trypanosoma soluble extract and with neutralizing monoclonal anti‐mTNF antibodies. Treatment of the infected animals with different doses of T. brucei soluble extract resulted in a lower first parasitaemia peak (low ...
Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock protein 72 in human peripheral blood mononuclear cells.
The adaptor molecule Lnk negatively regulates tumor necrosis factor-alpha-dependent VCAM-1 expression in endothelial cells through inhibition of the ERK1 and -2 pathways. J Biol Chem. 2006 Jul 21; 281(29):20148-59 ...
A number of recombinant plasmids coding for fusion proteins between human interferon-gamma (IFN-gamma) and human tumour necrosis factor alpha (TNF alpha) or beta (TNF beta) were constructed by using site-directed mutagenesis and ligation of the respective genes. In these proteins the whole IFN-gamma sequence of the molecule is linked at the N terminus via a short polypeptide linker to the TNF alpha sequence lacking two N-terminal amino acid residues or to the whole TNF beta sequence. A series of mutants with deletions in the interferon part of the fusion proteins were also produced. All the fusion genes obtained were efficiently expressed in Escherichia coli under the control of early promoters of bacteriophage T7. The recombinant fusion proteins were found to be unstable inside bacterial cells. Bacterial cell lysates expressing these fusion genes or their deletion mutants showed both biological activities in vitro: the antiviral activity of IFN-gamma and the cytotoxic activity of TNF.
Background: The tumor necrosis factor alpha (TNFα) is a cytokine that produced principally by monocyte/macrophages and T lymphocytes, respectively. TNFα is recognized as the primary mediator of immunity in inflammation reaction. One important application of Tumor Necrosis Factor Receptor 2 (TNFR2) is for the treatment of autoimmune diseases like rheumatoid arthritis (RA). Objectives: The aim of this study is to examine the therapeutic trace of the recombinant humanTNFR2 on collagen-induced arthritis (CIA) in mice. Materials and Methods: CIA was created in 20 mice by immunization with bovine type II collagen (CII). After the mice were boosted on day 21, they were injected with the recombinant protein in test group (1 and assessed edema in paws and knee joints after two weeks. The quantities of inflammatory cytokines such as TNF-α, interleukin-1 beta (IL-β1), interleukin-6 (IL-6), and interleukin-10(IL-10) in serum were evaluated through enzyme-linked immunosorbent assay (ELISA) kit. In
Tumor necrosis factor alpha (TNF-alpha) is a cytokine that belongs to the tumor necrosis factor (TNF) superfamily. TNF-alpha is mainly secreted by macrophages. TNF-alpha is involved in the regulat...
TY - JOUR. T1 - Tumor necrosis factor-α and interleukin-1β production by human fetal Kupffer cells. AU - Kutteh, William H.. AU - Rainey, William E.. AU - Beutler, Bruce. AU - Carr, Bruce R.. PY - 1991/7. Y1 - 1991/7. N2 - This study describes the isolation and characterization of human fetal Kupffer cells. We demonstrated that these cells have the potential to respond to cytokines and lipopolysaccharide with an increased production of tumor necrosis factor-α and interleukin-1β. Kupffer cells were characterized by: (1) morphologic characteristics after adherence to plastic, (2) staining for α-naphthyl acetate esterase, (3) immunofluorescence with monoclonal antibodies, and (4) phagocytosis of latex beads. More than 90% of the adherent cells were identified as macrophages. Kupffer cells cultured with lipopolysaccharide were able to produce interleukin-1β and tumor necrosis factor-α in a time- and dose-dependent fashion and maximal secretion was observed with the use of 10 μg of ...
TNF-alpha is a highly pleiotropic cytokine and plays an important role in regulating HIV-1 replication. It may compromise the integrity of the blood-brain-barrier and, thus, may contribute to the neurotoxicity of HIV-1-infection. Both intravenous drug abuse (IDU) and HIV infection can increase TNF-alpha activity, but little information is available on the effects of a combination of these factors on TNF-alpha. We investigated plasma TNF-alpha levels and mRNA in the peripheral monocytes of 166 men and women in three groups: HIV-1-positive IDUs, HIV-1-negative IDUs, and HIV-negative non-IDU control participants. HIV-1-positive IDUs had higher TNF-alpha levels than HIV-1-negative IDUs who, in turn, had higher levels than controls. TNF-alpha mRNA expression in peripheral monocytes was significantly increased in both HIV-1-positive and negative IDUs compared to controls. These findings show that the effects of HIV infection and intravenous drug use may be additive in increasing TNF-alpha levels. Given the
TY - JOUR. T1 - WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-α (TNF-α)-stimulated cardiac fibroblast proliferation but inhibits TNF-α-induced cardiomyocyte death. AU - Venkatachalam, Kaliyamurthi. AU - Venkatesan, Balachander. AU - Valente, Anthony J.. AU - Melby, Peter. AU - Nandish, Sailesh. AU - Reusch, Jane E B. AU - Clark, Robert A.. AU - Chandrasekar, Bysani. PY - 2009/5/22. Y1 - 2009/5/22. N2 - WNT1-inducible signaling pathway protein-1 (WISP1), a member of the CYR61/CTGF/Nov family of growth factors, can mediate cell growth, transformation, and survival. Previously we demonstrated that WISP1 is up-regulated in post-infarct heart, stimulates cardiac fibroblast proliferation, and is induced by the proinflammatory cytokine tumor necrosis factor-α (TNF-α). Here we investigated (i) the localization of TNF-α and WISP1 in post-infarct heart, (ii) the mechanism of TNF-α-mediated WISP1 induction in primary human cardiac fibroblasts (CF), (iii) the role of ...
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BACKGROUND: Because traditional therapies for rheumatoid arthritis (RA) such as methotrexate (MTX) do not produce an adequate response in many patients, newer therapies that block the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are increasingly being used in combination with MTX.. OBJECTIVE: This study evaluated the efficacy, pharmacokinetics, and safety profile of adalimumab, a fully human anti-TNF alpha monoclonal antibody, when added to continuing MTX therapy.. METHODS: This Phase I, randomized, dose-titration study consisted of a 4-week, double-blind, placebo-controlled treatment phase and a 26-month, open-label continuation phase. Patients with RA who had been taking stable doses of MTX (mean dose, 17 mg/wk) for , or =3 months before enrollment with an inadequate response were randomly assigned to receive 2 single doses of either adalimumab 0.25, 0.5, 1, 3, or 5 mg/kg i.v. or placebo in the double-blind phase. In the open-label phase, patients received treatment with 1 ...
Tumor necrosis factor (TNF) is a cytokine that promotes inflammation and contributes to pathogenesis of inflammatory bowel diseases. Unlike other cells and tissues, intestinal epithelial cells undergo rapid cell death upon exposure to TNF, by unclear mechanisms. We investigated the roles of inhibitor of apoptosis proteins (IAPs) in the regulation of TNF-induced cell death in the intestinal epithelium of mice and intestinal organoids.RNA from cell lines and tissues was analyzed by quantitative polymerase chain reaction, protein levels were analyzed by immunoblot assays. BIRC2 (also called cIAP1) was expressed upon induction from lentiviral vectors in young adult mouse colon (YAMC) cells. YAMC cells, the mouse colon carcinoma cell line MC38, the mouse macrophage cell line RAW 264.7, or mouse and human organoids were incubated with second mitochondrial activator of caspases (Smac)-mimetic compound LCL161 or recombinant TNF-like weak inducer of apoptosis (TNFSF12) along with TNF, and cell death was ...
Tumor necrosis factor (TNF) alpha has been shown to be a major therapeutic target in rheumatoid arthritis with the success of anti-TNFalpha antibody clinical trials. Although signaling pathways leading to TNFalpha expression have been studied in some detail, there is evidence for considerable differences between individual cell types. This prompted us to investigate the intracellular signaling pathways that result in increased TNFalpha synthesis from macrophages in the diseased synovial joint tissue. Using an adenoviral system in vitro we report the successful delivery of genes to more than 95% of normal human macrophages. This permitted us to show, by using adenoviral transfer of IkappaB alpha, the natural inhibitor of NF-kappaB, that induction of TNFalpha in normal human macrophages by lipopolysaccharide, but not by some other stimuli, was inhibited by 80%. Furthermore the spontaneous production of TNFalpha from human rheumatoid joint cell cultures was inhibited by 75%, indicating that the NF-kappaB
Previous studies in the laboratory have shown that the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA). The mechanisms involved in regulating monocyte/macrophage cytokine production are not yet fully understood, but are thought to involve both soluble factors and cell/cell contact with other cell types. We and others have previously demonstrated that T cells activated through the T cell receptor/CD3 complex induce monocyte TNF-alpha production by contact-mediated signals. In this report, we investigated further whether T cells activated by cytokines in the absence of T cell receptor stimulation also regulate monocyte cytokine production. T cells were activated in an antigen-independent manner using the cytokines interleukin (IL)-15 or IL-2 alone, or in combination with IL-6 and TNF-alpha. Subsequently, T cells were fixed and incubated with monocytes. Fixed, cytokine-stimulated T cells induced monocytes to secrete TNF-alpha
TNF-alpha increases the local estrogen biosynthesis in human endometrial glandular cells and directs estrogen metabolism into more hormonally active and carcinogenic metabolites. These effects may impact many physiological and pathological processes that occur within the endometrium.
We describe here a monoclonal antibody (H398) that immunoprecipitates a human 60-kD tumor necrosis factor (TNF) membrane receptor (p60) and competes with TNF binding to p60 but not to p85 TNF receptors. Despite partial inhibition of TNF binding capacity of cells coexpressing both TNF receptor molecules, H398 uniformly and completely inhibits very distinct TNF responses on a variety of cell lines. These data suggest a limited structural heterogeneity in those components actually contributing to TNF responsiveness and identify p60 as a common receptor molecule essential for TNF signal transduction. As H398 is a highly effective TNF antagonist in vitro, it might be useful as a therapeutic agent in the treatment of TNF-mediated acute toxicity. ...
A B Millar, R F Miller, N M Foley, G A W Rook, S J G Semple; Tumour Necrosis Factor (Tnf Alpha) Production by Peripheral Blood Monocytes and Alveolar Macrophages from Patients with Hiv-Related Lung Disease. Clin Sci (Lond) 1 January 1990; 78 (s22): 17P. doi: Download citation file:. ...
Results: We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p,0.05 ...
TY - JOUR. T1 - Interleukin‐1 and tumor necrosis factor production by tumor‐associated mononuclear leukocytes and peripheral mononuclear leukocytes in cancer patients. AU - Economou, James S.. AU - Colquhoun, Steven D. AU - Anderson, Timothy M.. AU - McBride, William W.. AU - Golub, Sidney. AU - Holmes, E. Carmack. AU - Morton, Donald L.. PY - 1988/1/1. Y1 - 1988/1/1. N2 - The production of interleukin‐I (IL‐I) and tumor necrosis factor (TNF) by tumor‐associated mononuclear leukocytes (TAML) and peripheral mononuclear leukocytes (PBML) from 9 otherwise untreated patients with a variety of malignancies (lung, sarcoma, stomach, renal) was assessed. Cells were cultured for 24 hr in vitro in the presence or absence of lipopolysaccharide (LPS), and IL‐I and TNF levels were measured in culture supernatants. TNF production was comparable between TAMLs and PBMLs. However, a striking defect in IL‐I production by TAMLs was noted. There was no basal production of IL‐I and LPS‐stimulated ...
TY - JOUR. T1 - An inducible autocrine cascade regulates rat hepatocyte proliferation and apoptosis responses to tumor necrosis factor-α. AU - Cosgrove, Benjamin D.. AU - Cheng, Connie. AU - Pritchard, Justin R.. AU - Stolz, Donna B.. AU - Lauffenburger, Douglas A.. AU - Griffith, Linda G.. PY - 2008/7/1. Y1 - 2008/7/1. N2 - Tumor necrosis factor-α (TNF) is an inflammatory cytokine that induces context-dependent proliferation, survival, and apoptosis responses in hepatocytes. TNF stimulates and enhances growth factor-mediated hepatocyte proliferation and survival following partial hepatectomy, but also acts in concert with other inflammatory cytokines of the innate immune response during viral infection to induce apoptosis in hepatocytes. In other epithelial cell types, TNF has recently been shown to stimulate autocrine release of transforming growth factor-α (TGF-α) and interleukin-1 (IL-1) family ligands. Here, we examine the role of these autocrine ligands in modulating TNF-induced ...
Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting. ...
Distributions of tumor necrosis factor (TNF) and its soluble receptor forms, R55-BP and R75-BP, were analyzed in the cerebrospinal fluid of patients with severe acute or chronic central nervous system infections. Tuberculous infections were associated with high ratios of R55-BP and R75-BP to TNF, 27.2 and 28.0, respectively, suggesting a small biologically active fraction of TNF. The opposite was found in subjects with acute bacterial meningitis. They had large fractions of biologically active TNF and thus low ratios of R55-BP and R75-BP to TNF, 3.7 and 4.0, respectively. It is hypothesized that chronic infectious diseases, such as tuberculous infections, may be associated with inadequate production of TNF and a concomitant relative increase of soluble TNF receptors, which may prolong the disease ...
TY - JOUR. T1 - Associations between tumor necrosis factor-α polymorphisms and susceptibility to pulmonary tuberculosis. T2 - Meta-analysis. AU - Lee, Young Ho. AU - Song, Gwan Gyu. PY - 2015/7/31. Y1 - 2015/7/31. N2 - The aim of this study was to determine whether tumor necrosis factor-α (TNF-α) polymorphisms are associated with susceptibility to pulmonary tuberculosis (PTB) in different ethnic populations. MEDLINE and Embase databases and manual searches were employed to identify articles in which TNF-α polymorphisms were determined in patients with PTB and controls. A meta-analysis was conducted on the associations of the TNF-α -308A/G, -238A/G, and -857T/C polymorphisms with PTB susceptibility. A total of 13 studies met the inclusion criteria, including 12, 6, and 4 studies on TNF-α-308A/G, -238A/G, and -857T/C polymorphisms, respectively. Meta-analysis showed no association between the TNF-α -308A allele and PTB susceptibility in all study subjects (odds ratio, OR = 1.182, 95%CI = ...
TY - JOUR. T1 - Placental tumor necrosis factor-α protein expression during normal human gestation. AU - Basu, Jayasri. AU - Agamasu, Enyonam. AU - Bendek, Bolek. AU - Salafia, Carolyn M.. AU - Mishra, Aruna. AU - Benfield, Nerys C.. AU - Prasad, Priya. AU - Mikhail, Magdy. PY - 2016/3/14. Y1 - 2016/3/14. N2 - Objective: Placental tumor necrosis factor-α (TNF-α) is a cell signaling protein. During pregnancy, TNF-α induces synthesis of matrix metalloproteinases (MMPs) which allows cytotrophoblasts to reach the spiral arteries deeper within the uterine decidua. TNF-α also augments apoptosis of vascular smooth muscle cells surrounding these arteries. In this study, chorionic villi TNF-α protein expression throughout normal human gestation were investigated. Methods: Placental chorionic villi tissues obtained from elective surgical terminations of pregnancy and from uncomplicated term births were assayed using EIA kits (Cayman Chemicals, Ann Arbor, MI, Item # 589201). Results: The median, 25th ...
Transcriptional activity of tumor necrosis factor-alpha gene in peripheral blood mononuclear cells in patients with coronary slow flow
The anti-tumor activity of recombinant human tumor necrosis factor (rHTNF) was examined against four newly induced murine sarcomas (MCA-101, -102, -105, and -106) and a murine adenocarcinoma (MCA-38) transplanted s.c. into C57BL/6 mice. The serum half-life after a single i.v. injection of rHTNF was determined to be 30 +/- 2 min. Tumor-bearing mice were more susceptible to the toxic side effects of rHTNF than were normal mice. Forty-eight percent (41/86) of tumor bearing animals that received 10 micrograms rHTNF died within 48 hr after treatment compared with no deaths in 28 normal animals receiving this dose. Treatment of mice bearing either the MCA-101, -102, -105, or -106 sarcoma or the MCA-38 adenocarcinoma with rHTNF resulted in a marked necrosis of the central portion of each tumor within 24 hr. Animals bearing the weakly immunogenic tumors MCA-105, -106, and -38 experienced a reduction in average tumor area of 47% +/- 5, 46% +/- 6, and 37% +/- 11, respectively, by 3 to 4 days after ...
Tumor necrosis factor-alpha is released from cells by a proteolytic cleavage. Previous work suggested that a specific, non-matrix metalloproteinase carries out this cleavage, but matrix metalloproteinases have also been implicated. In this paper, we report that none of the matrix metalloproteinases tested cleaved peptide substrates as specifically as the non-matrix metalloproteinase. A matrix metalloproteinase did process tumor necrosis factor-alpha extracted from COS cells, but neither tissue inhibitor of metalloproteinases-1 nor -2 blocked tumor necrosis factor-alpha processing by human monocytes. Moreover, tissue inhibitor of metalloproteinases-1 had at most a partial effect on the in vivo release of the cytokine in mice. We conclude that a non-matrix metalloproteinase is the major physiological tumor necrosis factor-alpha convertase.
Tumor necrosis factor-alpha is released from cells by a proteolytic cleavage. Previous work suggested that a specific, non-matrix metalloproteinase carries out this cleavage, but matrix metalloproteinases have also been implicated. In this paper, we report that none of the matrix metalloproteinases tested cleaved peptide substrates as specifically as the non-matrix metalloproteinase. A matrix metalloproteinase did process tumor necrosis factor-alpha extracted from COS cells, but neither tissue inhibitor of metalloproteinases-1 nor -2 blocked tumor necrosis factor-alpha processing by human monocytes. Moreover, tissue inhibitor of metalloproteinases-1 had at most a partial effect on the in vivo release of the cytokine in mice. We conclude that a non-matrix metalloproteinase is the major physiological tumor necrosis factor-alpha convertase.
Mutations in MECP2 cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of MECP2 also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MeCP2 in controlling immune and inflammatory responses. Here, we used mecp2-null zebrafish to study the potential function of Mecp2 as an immunological regulator. Mecp2-deficiency resulted in an increase in neutrophil infiltration and upregulated expression of the pro- and anti-inflammatory cytokines Il1b and Il10 as a secondary response to disturbances in tissue homeostasis. In contrast, expression of the pro-inflammatory cytokine tumor necrosis factor alpha (Tnfa) was consistently downregulated in mecp2--null animals during development, representing the earliest developmental phenotype described for MeCP2-deficiency to date. Expression of tnfa was unresponsive to inflammatory stimulation, and was partially restored by re-expression of functional mecp2. Thus, Mecp2 is ...
TY - JOUR. T1 - Nitric oxide modulates interleukin-1β and tumour necrosis factor-α synthesis, and disease regression by alveolar macrophages in pulmonary tuberculosis. AU - Wang, Chun Hua. AU - Kuo, Han Pin. PY - 2001/5/9. Y1 - 2001/5/9. N2 - Pretreatment with nitric oxide synthase (NOS) inhibitors profoundly increases mortality, bacterial burden and pathological tissue damage in mice infected with Mycobacterium tuberculosis. Nitric oxide (NO) production is enhanced in alveolar macrophages (AM) of tuberculosis (TB) patients. Interleukin (IL)-1β and tumour necrosis factor (TNF)-α released from AM are involved in the immune response to mycobacterial infection. The aim of the present study was to examine whether NO is implicated in IL-1β and TNF-α synthesis by AM and related to the resolution of disease activity in TB patients. Purified AM were retrieved by bronchoalveolar lavage from TB patients and normal subjects, and cultured in the presence or absence of a NO inhibitor, ...
AIM Behcets disease (BD) is a systemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress. ...
In many different cell types, pro-inflammatory agonists induce the expression of cyclooxygenase 2 (COX-2), an enzyme that catalyzes rate-limiting steps in the conversion of arachidonic acid to a variety of lipid signaling molecules, including prostaglandin E₂ (PGE₂). PGE₂ has key roles in many early inflammatory events, such as the changes of vascular function that promote or facilitate leukocyte recruitment to sites of inflammation. Depending on context, it also exerts many important anti-inflammatory effects, for example increasing the expression of the anti-inflammatory cytokine interleukin 10 (IL-10), and decreasing that of the pro-inflammatory cytokine tumor necrosis factor (TNF). The tight control of both biosynthesis of, and cellular responses to, PGE₂ are critical for the precise orchestration of the initiation and resolution of inflammatory responses. Here we describe evidence of a negative feedback loop, in which PGE₂ augments the expression of dual specificity phosphatase 1, ...
OBJECTIVE: To investigate the hypothesis that tumor necrosis factor alpha (TNFalpha) blockade in rheumatoid arthritis (RA) diminishes synovial synthesis of TNFalpha, interleukin-1alpha (IL-1alpha), and IL-1beta. METHODS: Patients with active RA received a single 10 mg/kg infusion of infliximab.
Fingerprint Dive into the research topics of The role of tumour necrosis factor-α and tumour necrosis factor receptor signalling in inflammation-associated systemic genotoxicity. Together they form a unique fingerprint. ...
High-density lipoproteins (HDL) levels have been shown to be inversely correlated with coronary heart disease, but the mechanisms of the direct protective effect of HDL on endothelial cells are not fully understood. The apoptosis of endothelial cells induced by cytokines and/or oxidized low-density …
The Effect of Smoking on Response to Tumour Necrosis Factor-Alpha Inhibitor Treatment in Psoriatic Arthritis Patients: Results from the TURKBIO Registry ...
TY - JOUR. T1 - A novel tumor necrosis factor-mediated mechanism of direct epithelial sodium channel activation. AU - Czikora, István. AU - Alli, Abdel. AU - Bao, Hui Fang. AU - Kaftan, David. AU - Sridhar, Supriya. AU - Apell, Hans Jürgen. AU - Gorshkov, Boris. AU - White, Richard. AU - Zimmermann, Astrid. AU - Wendel, Albrecht. AU - Pauly-Evers, Meike. AU - Hamacher, Jürg. AU - Garcia-Gabay, Irène. AU - Fischer, Bernhard. AU - Verin, Alexander. AU - Bagi, Zsolt. AU - Pittet, Jean Francois. AU - Shabbir, Waheed. AU - Lemmens-Gruber, Rosa. AU - Chakraborty, Trinad. AU - Lazrak, Ahmed. AU - Matthay, Michael A.. AU - Eaton, Douglas C.. AU - Lucas, Rudolf. PY - 2014/9/1. Y1 - 2014/9/1. N2 - Rationale: Alveolar liquid clearance is regulated by Na+ uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na+-K+-ATPase in type II alveolar epithelial cells. Dysfunction of these Na+ transporters during pulmonary inflammation can contribute to pulmonary ...
Phase I trial of recombinant human gamma-interferon and recombinant human tumor necrosis factor in patients with advanced gastrointestinal cancer.
The chromatographic behaviour of recombinant human tumour necrosis factor beta (rhTNF-β) (pI ~9.0) during cation-exchange chromatography at pH 7.5 is investigated. Without prior treatment of the Escherichia coli cell extract with polyethyleneimine (PEI), very little rhTNF-β was bound to the column. However, upon addition of 5% PEI (100 μl ml-1) to the cell lysate, rhTNF-β was shown to bind to cation-exchange columns normally. TNF-β was readily precipitated from the clarified cell extract by 20% ammonium sulphate, but only ca. 25% of this precipitate could be re-solubilized for further purification. However, when 5% PEI was included in the solubilization buffer, the balance of the rhTNF-β could be recovered. It is proposed that charge interaction between rhTNF-β and nucleic acids in the cell extract is responsible for both of these anomalous phenomena, and that PEI (a cationic polyelectrolyte) was able to disrupt this interaction by displacing rhTNF-β from the charge complex ...
Incubation of the human U937 histiocytic lymphoma cell line with granulocyte-macrophage colony stimulating factor (GM-CSF) rendered the cells responsive to induction of TNF by LPS. Treatment with IL-6 reduced TNF production in GM-CSF-primed U937 cells. The inhibitory effect was most pronounced (approximately equal to 80%) when IL-6 was added either along with GM-CSF or within the first 3 h of GM-CSF treatment. Both GM-CSF or IL-6 inhibited [3H]TdR uptake in U937 cells, and simultaneous treatment with GM-CSF and IL-6 resulted in an additive inhibitory effect on cell proliferation. However, the inhibition of TNF production could not be explained by the inhibitory effect of IL-6 on cell growth, nor was it due to a reduction in cell viability. An inhibition of TNF production by IL-6 was also demonstrated in cultured human peripheral blood monocytes. Treatment with IL-6 also resulted in a dose-dependent reduction of the 17-kDa TNF band revealed by SDS-PAGE after labeling monocytes with [35S]cysteine ...
Looking for online definition of tumor necrosis factor-alpha (alpha) in the Medical Dictionary? tumor necrosis factor-alpha (alpha) explanation free. What is tumor necrosis factor-alpha (alpha)? Meaning of tumor necrosis factor-alpha (alpha) medical term. What does tumor necrosis factor-alpha (alpha) mean?
Tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) are pluripotent cytokines and have multiple functions during the inflammatory response. Using a murine model of autoimmune myocarditis, we studied the role of TNF and IFN-gamma in myocardial inflammation. Neutralizing monoclonal antibodies against TNF-alpha/beta and IFN-gamma were administered to myosin-immunized A/J mice to assess the effect on the severity of myocardial inflammation. Anti-TNF treatment significantly reduced the severity of myocarditis compared with rat immunoglobulin G or saline controls (p less than 0.0007) when given before myosin immunization. Myosin-specific lymph node T-cell proliferation studies showed no difference in the proliferative response between the anti-TNF-treated mice and controls. Administration of anti-TNF to mice after myosin immunization had no effect on the severity of inflammation. This suggests that TNF is an important mediator early in the pathogenesis of myocardial inflammation in this model ...
TY - JOUR. T1 - Tumor necrosis factor-α is not essential in endotoxin induced eye inflammation. T2 - Studies in cytokine receptor deficient mice. AU - Rosenbaum, James T.. AU - Han, Young Bok. AU - Park, Jong Moon. AU - Kennedy, Michael. AU - Planck, Stephen R.. N1 - Copyright: Copyright 2007 Elsevier B.V., All rights reserved.. PY - 1998/12. Y1 - 1998/12. N2 - Objective. Anterior uveitis frequently occurs in association with specific systemic inflammatory diseases. Interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-α) have been implicated in the pathogenesis of these diseases. We evaluate the need for these cytokines in a model of anterior uveitis. Methods. Endotoxin was injected into the vitreous of mice deficient in IL-1 receptor type I, TNF receptors p55 and p75, both IL-1R1 and TNFR p55, or controls. Eyes were harvested after 24 h for histology and IL-6 bioassays or after 3 h for reverse transcriptase-polymerase chain reaction analysis of mRNA for specific cytokines or enzymes. ...
TY - JOUR. T1 - Protective effect of etanercept, an inhibitor of tumor necrosis factor-α, in a rat model of retinal ischemia. AU - Bae, Hyoung Won. AU - Lee, Naeun. AU - Seong, Gong Je. AU - Rho, Seungsoo. AU - Hong, Samin. AU - Kim, Chan Yun. N1 - Publisher Copyright: © 2016 Bae et al.. PY - 2016/6/4. Y1 - 2016/6/4. N2 - Background: To assess the neuroprotective effect of etanercept (Enbrel®) which is a commercialized Tumor necrosis factor-α (TNF-α) inhibitor on axonal injury in an animal model of acute ischemia. Methods: Acute ischemia was induced by intraocular pressure elevation in 36 rats. The treatment groups underwent subcutaneous injection of etanercept (0.3 or 1.0 mg/kg) three times per week up to 4 weeks. The control groups were treated in the same manner using the same volume of phosphate-buffered saline (PBS). Optic nerve damage was evaluated by counting the number of axons under a transmission electron microscope. Microglial cell activity was assessed using Iba1 and CD68. ...
TY - JOUR. T1 - Tumor necrosis factor-α is decreased in the umbilical cord plasma of patients with severe preeclampsia. AU - Kupferminc, Michael J.. AU - Peaceman, Alan M.. AU - Dollberg, Shaul. AU - Socol, Michael L.. PY - 1999/1/1. Y1 - 1999/1/1. N2 - We investigated the role of the fetal immune system in pregnancies complicated by preeclampsia by assessing umbilical cord plasma levels of the cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Nineteen nulliparous patients with severe preeclampsia composed the study group (group A). A comparison group was comprised of 19 healthy nulliparous patients with uneventful pregnancies (group B). Mixed umbilical cord blood was collected immediately after delivery. Plasma was prepared and all samples were assayed for TNF-α and IL-1β by specific enzyme-linked immunoassays (ELISAs). Data are presented as the median with range of values. The length of labor was similar in both groups. TNF-α was detected less frequently in the ...
TY - JOUR. T1 - Comparison of tumor necrosis factor-α effect on the expression of iNOS in macrophage and cardiac myocytes. AU - Sanders, D. Bradford. AU - Larson, Douglas F.. AU - Hunter, Kyler. AU - Gorman, Mark. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2001/1. Y1 - 2001/1. N2 - Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), are elevated during cardiopulmonary bypass (CPB), heart failure, and inflammatory cardiac and systemic diseases. Elevated TNF-α has been linked to diminished cardiac function, decreased systemic vascular resistance, as well as renal and pulmonary dysfunction. It is understood that myocardial tissues can express TNF-α, which results in the induction of inducible nitric oxide synthase (iNOS) leading to a significant decline in cardiac function and other direct effects. The hypothesis of this study was to determine if TNF-α would stimulate iNOS and its product nitric oxide (NO) similarly in immortalized macrophage ...
TY - JOUR. T1 - Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF). T2 - Similarities between TNF-α and interleukin. AU - Jacob, Chaim O.. AU - Aiso, Sadakazu. AU - Michie, Sara A.. AU - Mcdevitt, Hugh O.. AU - Acha-Orbea, Hans. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 1990. Y1 - 1990. N2 - The role of tumor necrosis factor α (TNF-α) in the pathogenesis of autoimmune diabetes mellitus was tested in the nonobese mouse (NOD) model system. The effects of TNF-α were assessed on three levels: (i) insulitis development, (ii) development of overt diabetes, (iii) adoptive transfer of diabetes by splenic lymphocytes. Spontaneous diabetes mellitus was blocked in NOD mice by long-term treatment with recombinant TNF-α. Treatment with TNF-α caused a significant reduction in the lymphocytic infiltration associated with the destruction of the insulin-producing beta cells. Class II major histocompatibility complex la expression by islet cells ...
TY - JOUR. T1 - The inhibition in tumor necrosis factor-α-induced attenuation in endothelial thrombomodulin expression by carvedilol is mediated by nuclear factor-κB and reactive oxygen species. AU - Lin, Pen-Yuan. AU - Shen, Hsi Che. AU - Chen, Chien Jen. AU - Wu, Shu En. AU - Kao, Hsien Li. AU - Huang, Jen-Hung. AU - Wang, Danny Ling. AU - Chen, Shih-Chung. PY - 2010/1. Y1 - 2010/1. N2 - Carvedilol, a nonselective β-adrenoceptor antagonist, has been shown to possess antioxidant effects and reduce the risk of hospitalization and death in patients with severe congestive heart failure, which is featured by the activation of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), and leads to thrombotic complications. Thrombomodulin (TM) plays protective roles against thrombosis. Treatment of ECs with TNF-α resulted in a down-regulation in the TM expression in a time-dependent manner. Pre-treatment of ECs with carvedilol (1 and 10 μM) for 1 h significantly up-regulated the TM ...
TY - JOUR. T1 - Effects of tumor necrosis factor-α on cell proliferation, prostaglandins and matrix-metalloproteinases production in rat endometrial stromal cells cultured in vitro. AU - Gamo, Toru. AU - Yamauchi, Nobuhiko. AU - Nishimura, Kyohei. AU - Watanabe, Ryo. AU - Matsumoto, Kenji. AU - Oozono, Shinji. AU - Kubota, Kaiyu. AU - He, Pei Jian. AU - Soh, Tomoki. AU - Hattori, Masa Aki. PY - 2007/12/1. Y1 - 2007/12/1. N2 - Tumor necrosis factor-α (TNF-α) is known as a pluripotent cell mediator, and it is implicated in the control of uterine cell growth, differentiation and function during estrous cycle and pregnancy. In this study, we investigated the effect of TNF-α on endometrial stromal cells derived from rat uterus (rat endometrial stromal cells, RES). RES were isolated from rat endometrium at day 5 of pregnancy. Proliferation activities of RES were measured by using bromodeoxyuridine (BrdU) labeling kit, the productions of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF 2α) were ...
TY - JOUR. T1 - Tumor necrosis factor-α modulates epithelial mesenchymal transition mediators ZEB2 and S100A4 to promote cholangiocarcinoma progression. AU - Techasen, Anchalee. AU - Namwat, Nisana. AU - Loilome, Watcharin. AU - Duangkumpha, Kassaporn. AU - Puapairoj, Anucha. AU - Saya, Hideyuki. AU - Yongvanit, Puangrat. PY - 2014/9. Y1 - 2014/9. N2 - Background The epithelial-mesenchymal transition (EMT) process strongly contributes to cancer metastasis. This study was to investigate the alteration of EMT-related proteins (ZEB1, ZEB2 and S100A4) in cholangiocarcinoma (CCA) tissues. The effect of tumor necrosis factor-α (TNF-α) on the expression of those molecules in CCA cells was investigated. Methods The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was used to quantify ZEB1, ZEB2 and S100A4 mRNA levels in 50 CCA tissues and related its expression to clinicopathological data. ZEB2 protein immunostaining was investigated in 165 CCA tissues. The effect of ...
TY - JOUR. T1 - Effects of tumor necrosis factor-α on podocyte expression of monocyte chemoattractant protein-1 and in diabetic nephropathy. AU - Chung, Choon Hee. AU - Fan, Jingyi. AU - Lee, Eun Young. AU - Kang, Jeong Suk. AU - Lee, Seung Joo. AU - Pyagay, Petr E.. AU - Khoury, Charbel C.. AU - Yeo, Tet Kin. AU - Khayat, Mark F.. AU - Wang, Amy. AU - Chen, Sheldon. N1 - Publisher Copyright: © 2015 S. Karger AG, Basel.. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Background/Aims: Tumor necrosis factor (TNF)-α is believed to play a role in diabetic kidney disease. This study explores the specific effects of TNF-α with regard to nephropathy-relevant parameters in the podocyte. Methods: Cultured mouse podocytes were treated with recombinant TNF-α and assayed for production of monocyte chemoattractant protein-1 (MCP-1) by enzyme-linked immunosorbent assay (ELISA). TNF-α signaling of MCP-1 was elucidated by antibodies against TNF receptor (TNFR) 1 or TNFR2 or inhibitors of nuclear factor-kappaB ...
In this study, we explore the regulatory roles of pro-inflammatory cytokine tumor necrosis factor alpha (TNF) in the innate immunity of macrophages against B. abortus infection. We show that infection of macrophage with B. abortus induces marked expression and secretion of TNF which subsequently binds to TNF receptor 1 (TNFR-1) and activates a downstream signaling cascade of the innate immunity. Blocking of TNF signaling resulted in a notable increase of B. abortus survival which was associated with an increase of anti-inflammatory cytokine interleukin 10 (IL-10), a beneficial effector of Brucella survival, as well as remarkable decrease of reactive oxygen species (ROS) and nitric oxide (NO), antibrucella molecules ...
TY - JOUR. T1 - Tumor necrosis factor-α develops late anaphylactic reaction through cytosolic phospholipase A2 activation. AU - Kang, Nam In. AU - Kim, Hae Kyoung. AU - Ko, Hyun Mi. AU - Kim, Jae Hong. AU - You, Hye Jin. AU - Choi, Il Whan. AU - Im, Suhn Young. AU - Lee, Hern Ku. PY - 2008/11. Y1 - 2008/11. N2 - Background: We have recently reported that tumor necrosis factor (TNF)-α plays an important role in the development of a late anaphylactic reaction, but the downstream pathway beyond TNF-α remains unclear. Objective: It was the aim of this study to examine whether TNF-α induces late-phase anaphylaxis via the activation of cytosolic phospholipase A 2 (cPLA2). Methods: Using a murine model of active systemic anaphylaxis to penicillin V, the induction of the late phase of anaphylaxis was quantified by measuring the increase in hematocrit value as well as the plasma level of platelet-activating factor in TNF-α knockout mice. Phosphorylation of mitogen-activated protein kinases (MAPKs) ...
TY - JOUR. T1 - Persistent anti-inflammatory cytokine release in septic shock. AU - Sfeir, Tacla. AU - Saha, Dhanonjoy. AU - Astiz, Mark. AU - Rackow, Eric. PY - 1999/1/1. Y1 - 1999/1/1. N2 - Introduction: During septic shock dysregulation of monocyte cytokine release contributes to immunosuppression. We evaluated the difference in release of the pro-inflammatory cytokine tumor necrosis factor (TNF-α) and the anti-inflammatory cytokine interleukin 10 (IL-10) from blood monocytes isolated from healthy individuals and septic shock patients. Methods: Blood mononuclear cells from healthy volunteers (n=10, Normal) and septic shock patients (n=10, SS) were isolated and cultured. Culture plate adherent monocytes were incubated with either medium (Control) or LPS (LPS) for 18 hours at 31°C. The supernatant was collected and analyzed for TNF-α and IL-10 by ELISA. Values are mean ± SEM, * p,0.05 vs. control Results TNF- α ng/ml Normal SS Control .54±.12 .82±.25 LPS 3.26±1* 1.26±.31 IL-10 pg/ml ...
TY - JOUR. T1 - Monoclonal anti-tumor necrosis factor antibody renders non-obese diabetic mice hypersensitive to irradiation and enhances insulitis development. AU - Jacob, Chalm O.. AU - Aiso, Sadakazu. AU - Schreiber, Robert D.. AU - Mcdevitt, Hugh O.. PY - 1992/5/1. Y1 - 1992/5/1. N2 - In attempt to evaluate biological roles of tumor necrosis factor (TNF), we studied the effects of anti-TNF mAb in non-obese diabetic (NOD) mice. Anti-murine TNF mAb rendered NOD mice hypersensitive to the lethal effects of radiation and prevented the reconstitution of lethally Irradiated mice with adoptively transferred lymphocytes. While TNF-α reduced the incidence of diabetes development in the adoptive transfer system even when given 6 days post-transfer, mAb to TNF could not reduce or increase the incidence of diabetes compared to control mice. Administration of TNF-α for 4 or 8 weeks significantly reduced the Incidence of spontaneous Insulitis in NOD mice, while antl-TNF mAb given for 8 weeks Increased ...
Crystals of tumor necrosis factor (TNF) have been obtained in two forms. Rhombohedral crystals grow in 1.8 to 2.0 M ammonium sulfite, pH 7.8 at 21 degrees C, and tetragonal crystals grow in 2.6 M magnesium sulfate, pH 5.5 at 25 degrees C. Analysis of TNF by isoelectric focusing under native and denaturing conditions indicates that TNF molecules exist as trimers in solution. The rhombohedral cachectin crystals belong to space group R3 and have unit cell constants a = b = c = 47.65 A and alpha = beta = gamma = 88.1 degrees. Density determinations and the space group indicate that the unit cell contains one 51,000-dalton trimer. These crystals are stable in the x-ray beam and diffract to at least 1.85 A but are apparently twinned by merohedry. The tetragonal crystals are space group P4(3)2(1)2 or its enantiomorph P4(1)2(1)2 and have unit cell constants a = b = 95.08, c = 117.49. The asymmetric unit contains one trimer; the crystals are stable in the x-ray beam and diffract to beyond 3 A ...
1. Bertone-Johnson ER. Chronic inflammation and premenstrual syndrome: a missing link found? J Womens Health (Larchmt). 2016 Sep;25(9):857-8. doi: 10.1089/jwh.2016.5937.. 2. Ezaki K, Motoyama H, Sasaki H. Immunohistologic localization of estrone sulfatase in uterine endometrium and adenomyosis. Obstet Gynecol. 2001 Nov;98(5 Pt 1):815-9.. 3. Gao L, Gu Y, Yin X. High serum tumor necrosis factor-alpha levels in women with polycystic ovary syndrome: a meta-analysis. PLoS One. 2016 Oct 20;11(10):e0164021. doi: 10.1371/journal.pone.0164021.. 4. Alpañés M, Fernández-Durán E, Escobar-Morreale HF. Androgens and polycystic ovary syndrome. Expert Rev Endocrinol Metab. 2012;7(1):91-102.. 5. Niswender GD, Juengel JL, Silva PJ, Rollyson MK, McIntush EW. Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev. 2000 Jan;80(1):1-29.. 6. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al. Executive Summary to EDC-2: The Endocrine Societys Second Scientific ...
Aged,Antibodies, Monoclonal/adverse effects,Antibodies, Monoclonal, Humanized,Antirheumatic Agents/*adverse effects,Arthritis, Rheumatoid/*drug therapy,Drug Eruptions/*etiology/pathology,Female,Granuloma Annulare/*chemically induced/pathology,Humans,Immunoglobulin G/adverse effects,Male,Middle Aged,Receptors, Tumor Necrosis Factor,Tumor Necrosis Factor-alpha/*antagonists & ...
This new market research report forecasts on Tumor Necrosis Factor Market providing complete market figures, consisting market size and estimation by Tumor Necrosis Factor Market application and products depending upon geographical location for the forecasting period 2017 to 2025. Further, the Tumor Necrosis Factor Market research report study also encompasses complete industry background, with Tumor Necrosis Factor Market drivers, competitive market dynamics, market restraints, market growth opportunities, industry challenges and critical success factors (CSFs). The Tumor Necrosis Factor Market research report examines top industry competitors, offering organization market share analysis and detailed outlines of these firms, with product benchmarking.. Browse Full Report Visit - Reasons to Buy This Report :. ...
Eosinophils play a central role in asthma. The present study was performed to investigate the effect of tumour necrosis factor-α (TNF-α) on longevity of isolated human eosinophils. In contrast to Fas, TNF-α inhibited eosinophil apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation assay and morphological analyses. The effect of TNF-α on eosinophil apoptosis was reversed by a TNF-α neutralising antibody. The anti-apoptotic effect of TNF-α was not due to autocrine release of known survival-prolonging cytokines interleukins 3 and 5 or granulocyte-macrophage-colony-stimulatin​gfactor as their neutralisation did not affect the effect of TNF-α. The anti-apoptotic signal was mediated mainly by the TNF-receptor 1. TNF-α induced phosphorylation and degradation of IκB and an increase in NF-κB DNA-binding activity. The survival-prolonging effect of TNF-α was reversed by inhibitors of NF-κB pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IκB kinase, ...
TY - JOUR. T1 - Tumor necrosis factor inhibitors in patients with Takayasu arteritis. T2 - Experience from a referral center with long-term followup. AU - Schmidt, Jean. AU - Kermani, Tanaz A.. AU - Bacani, A. Kirstin. AU - Crowson, Cynthia S.. AU - Matteson, Eric L.. AU - Warrington, Kenneth J.. PY - 2012/7/1. Y1 - 2012/7/1. N2 - Objective. To report a single-center experience with the use of tumor necrosis factor (TNF) inhibitors in patients with Takayasu arteritis (TA). Methods. We retrospectively studied a cohort of patients with refractory TA evaluated at our institution and treated with TNF inhibitors. American College of Rheumatology criteria for TA were used for inclusion. Disease activity was assessed according to the National Institutes of Health criteria. Results. We included 20 patients (19 women, 17 white) with a mean ± SD age of 33 ± 10.2 years and a median disease duration of 15.9 months (interquartile range [IRQ] 2-32.7 months) prior to the use of TNF inhibitors. Before the use ...
The rationale for anti-tumour necrosis factor-alpha (anti-TNFalpha) therapy in rheumatoid arthritis (RA) is based on experiments on cultures of human rheumatoidjoint tissue, supported by experiments in animal models, all of which demonstrated that anti-TNFalpha antibody had profound effects on the
C3a and C5a anaphylatoxins are two proinflammatory peptides generated during complement activation that act through distinct G$_i$ protein-coupled receptors named C3aR and C5aR, respectively. We have demonstrated previously that human astrocytes expressed C3aR and C5aR constitutively and were able to produce a functional complement. In this study, we examined the effect of an anaphylatoxin stimulation on cytokine expression by human astrocyte cell lines. Interleukin (IL)-1$\beta$, IL-6, tumor necrosis factor-\alpha$, and transforming growth factor-$\beta$ mRNA expression was studied by quantitative RT-PCR. Whereas IL-1$\beta$, tumor necrosis factor-$\alpha$, and transforming growth factor-$\beta$ mRNA levels remained unchanged, stimulation of astrocytoma cells (T98G, CB193, U118MG) by C3a, C5a, and peptidic C3aR and C5aR agonists induced an increase in the IL-6 mRNA level. The amount of IL-6 was markedly increased at 3 and 6 h and returned to the basal level at 9 h of stimulation. This response was
Effects of interferons and tumour necrosis factor-a on human lung cancer cell lines and the development of an interferon-resistant lung cancer cell line. ...
With the success of the human genome project, the focus of life science research has shifted to the functional and structural analyses of proteins, such as the fields of proteomics and structural genomics. These analyses of proteins, including newly identified proteins, are expected to contribute to the identification of therapeutically applicable proteins for various diseases. Thus, pharmacoproteomic-based drug discovery and the development of protein therapies has currently attracted a great deal of attention (1, 2, 3) . However, it is clinically difficult to use most bioactive proteins, such as tumor necrosis factor-α (TNF-α), as antitumor agents because of their very low stability and pleiotropic action in vivo (4 , 5) .. TNF-α was reported to exert a strong cytotoxicity to various kinds of tumor cells but not to normal cells in vitro and to cause hemorrhagic necrosis of certain transplanted solid tumors (6) . Thus, TNF-α has been considered a promising new drug for cancer therapy. On ...
The anti-inflammatory/antiallergic activity of a novel second-generation p38 mitogen-activated protein kinase inhibitor, SB 239063 [trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyridimidin-4-yl)imidazole], was investigated in vivo and in vitro. SB 239063 had an IC50 of 44 nM for inhibition of recombinant purified human p38α. In lipopolysaccharide-stimulated human peripheral blood monocytes, SB 239063 inhibited interleukin-1 and tumor necrosis factor-α production (IC50 values = 0.12 and 0.35 μM, respectively). A role for p38 kinase in cytokine-associated inflammation in the mouse was shown by p38 activation in the lung and inhibition of lipopolysaccharide-induced tumor necrosis factor-α production by SB 239063 (ED50 = 5.8 mg/kg p.o.). Antiallergic activity was demonstrated by essential abolition (∼93% inhibition) of inhaled ovalbumin (OA)-induced airway eosinophilia by SB 239063 (12 mg/kg p.o.), measured by bronchoalveolar lavage (BAL) in OA-sensitized mice. In addition, p38 ...
Listeriosis in mice with the severe combined immunodeficiency (SCID) mutation is an established model in vivo and in vitro of interferon gamma (IFN-gamma)-dependent macrophage activation by natural killer (NK) cells during the development of natural immunity. We demonstrate that IFN-gamma production from SCID splenocytes is stimulated by interleukin (IL) 12, tumor necrosis factor alpha (TNF-alpha), and IL-2 but is inhibited by IL-10, IL-10, IL-12, and TNF are induced by heat-killed Listeria monocytogenes (hk-LM) from SCID splenocytes and peritoneal macrophages. IL-12 production is necessary for hk-LM to stimulate IFN-gamma production by SCID splenocytes since neutralization of IL-12 totally blocks IFN-gamma production in this system. TNF-alpha and IL-2 act synergistically with IL-12 to augment IFN-gamma production. Also, exogenous IL-2 increases the response of NK cells to hk-LM or to IL-12 and TNF-alpha. In contrast, IL-10 inhibits hk-LM-induced IFN-gamma production at two levels: (i) by ...
Results: Atorvastatin significantly decreased liver transaminase, gamma-glutamyl transpeptidase, low-density lipoprotein-cholesterol, triglycerides, type IV collagen, and tumour necrosis factor-alpha levels, whilst it increased adiponectin and high-density lipoprotein-cholesterol. Atorvastatin improved nonalcoholic fatty liver disease activity score and increased liver to spleen density ratio. Multiple stepwise regression analysis revealed that gamma-glutamyl transpeptidase, tumour necrosis factor-alpha and liver to spleen density ratio ( inversely) were independently associated with nonalcoholic fatty liver disease activity score. Aspartate aminotransferase, low-density lipoprotein-cholesterol and nonalcoholic fatty liver disease activity score were independent determinants of decreased liver to spleen density ratio ...
Roh M, Zhang Y, Murakami Y, Thanos A, Lee SC, Vavvas DG, Benowitz LI, Miller JW. Etanercept, a widely used inhibitor of tumor necrosis factor-α (TNF-α), prevents retinal ganglion cell loss in a rat model of glaucoma. PLoS One 2012;7(7):e40065.
Severe infection and sepsis are common causes of morbidity and mortality. Early diagnosis in critically ill patients is important to reduce these complications. The present study was conducted to determine the role of serum leptin at early diagnosis and differentiation between patients with manifestations of systemic inflammatory response syndrome (SIRS) and those with sepsis in patients suffering from a broad range of diseases in the intensive care unit (ICU) and its correlation with other biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). One hundred and six adult ICU patients were observed. CRP, leptin, IL-6 and TNF-α were compared among the following groups: sepsis group (n = 40), SIRS group (n = 34) and non-SIRS group (n = 32). Patients were classified into these groups at the time of blood analysis for these biomarkers. Non-significant differences were observed among patients in different groups regarding biomarkers on the day of ICU
Vascular calcification is implicated in many diseases including atherosclerosis and diabetes. Tumor necrosis factor-α (TNF-α) has been shown to promote vascular calcification both in vitro and in vivo. However, the molecular mechanism of TNF-α-mediated vascular calcification has not yet been fully defined. Therefore, in this study, we aimed to investigate whether MSX2 acts as a crucial regulator in TNF-α-induced vascular calcification and to define the regulatory mechanism of MSX2 induction in human vascular smooth muscle cells (VSMCs ...
RPB499Hu01, CD120A; P55; TBP1; FPF; TNF-R; TNF-R-I; TNF-R55; TNFAR; TNFR1; TNFR55; TNFR60; P55-R; P60; Tumor necrosis factor receptor 1; Tumor necrosis factor-binding protein 1 | Products for research use only!
TY - JOUR. T1 - Role of tumor necrosis factor in preovulatory follicles of swine. AU - Prange-Kiel, J.. AU - Kreutzkamm, C.. AU - Wehrenberg, U.. AU - Rune, G. M.. PY - 2001. Y1 - 2001. N2 - The effects of tumor necrosis factor (TNF) on cultured porcine granulosa cells that were obtained from preovulatory follicles were studied with regard to following parameters: 1) TNF receptor type I expression, 2) progesterone receptor and transforming growth factor β receptor type II (TβR II) as markers of luteinization, 3) proliferation, and 4) apoptosis. For comparative purposes the effects of TNF were also studied on insulin/forskolin-treated cells, as this treatment is well established to induce luteinization. Cytochemical methods followed by semiquantitative analysis were used. Our data show that TNF treatment upregulates TNF receptor type I expression in granulosa cells. TNF downregulates the expression of TβR II of insulin/forskolin-stimulated and of unstimulated cells. The progesterone receptor ...
Tumour necrosis factor production by monocytes from cattle infected with Trypanosoma (Duttonella) vivax and Trypanosoma (Nannomonas) congolense STI possible association with severity of anaemia associated with the ...
1. The effects of recombinant human tumour necrosis factor alpha (TNF) and murine interleukin-1 alpha (IL-1) on the activation state of the hepatic pyruvate dehydrogenase complex (PDHa), the activity of mitochondrial PDH kinase, hepatic lipogenesis de novo and plasma triacylglycerol (TG) concentrations were studied. 2. Monokine effects depended upon prior nutritional state. In rats fasted for 20 h or 45 h before monokine administration and refeeding (orally or with intravenous glucose), PDHa, TG and hepatic lipogenesis were not increased. In rats fed ad libitum, treatment with TNF plus IL-1 increased the contribution of hepatic lipogenesis to circulating TG to 550% of control values (P = 0.03) and plasma TG concentrations to 159% (P = 0.02), whereas PDHa increased slightly to 120% (P = 0.02) and liver glycogen content fell to 45.8% (P = 0.05) of control values. 3. Intrinsic hepatic PDH kinase activity was not changed by monokine treatment in rats fed ad libitum. 4. The increased lipogenesis de ...
TY - JOUR. T1 - Anti-tumor necrosis factor-a treatment with infliximab for disseminated granuloma annulare. AU - Murdaca, Giuseppe. AU - Colombo, Barbara Maria. AU - Barabino, Gianfranco. AU - Caiti, Matteo. AU - Cagnati, Paola. AU - Puppo, Francesco. PY - 2010. Y1 - 2010. N2 - Granuloma annulare (GA) is a chronic inflammatory disease of unknown etiology characterized by the development of plaques preferentially localized to the distal extremities. Spontaneous remission and relapses are quite common and the course of GA is not easy to predict. Moreover, most therapeutic regimens have been used anecdotally and with variable success. We report the case of a 62-year-old White female patient affected by disseminated GA unsuccessfully treated with psoralen plus UVA photochemotherapy, prednisone, and cyclosporine (ciclosporin) who responded to the anti-tumor necrosis factor-a monoclonal antibody infliximab administered intravenously at a dosage of 5mg/kg at weeks 0, 2, and 6 and thereafter at monthly ...
TY - JOUR. T1 - Erythropoietin fails to reverse the anemia in mice continuously exposed to tumor necrosis factor-alpha in vivo. AU - Clibon, U.. AU - Bonewald, Lynda. AU - Caro, J.. AU - Roodman, G. David. PY - 1990. Y1 - 1990. N2 - Tumor necrosis factor-α (TNF) is a monokine produced by activated macrophages that has cytotoxic and cytostatic effects on erythroid progenitor cells. We have recently shown that Chinese hamster ovary cells transfected with the human TNF gene and which constitutively express TNF induced a hypoproliferative anemia, mild thrombocytopenia, and mild leukocytosis when injected into nude mice. We have used this murine model to determine if treatment with recombinant human erythropoietin can prevent or ameliorate the anemia seen with long-term continuous exposure to high concentrations of TNF. Mice bearing TNF-producing tumors became anemic with hematocrits ranging from 30 to 32%. Treatment with recombinant human erythropoietin (100-1000 U/kg body weight three times per ...
The genomic sequencing technique has been applied to assess the state of methylation in the DNA from human leukocyte subpopulations from healthy individuals and in the DNA from several individuals with myeloid or lymphatic leukemias or non-Hodgkin lymphomas. Leukocyte populations were purified by the high-gradient magnetic cell sorting technique. In the human tumor necrosis factor alpha (TNF-alpha) gene segment between nucleotides 300 and 1150, the specific methylation profile in the DNA from human granulocytes and monocytes is maintained in three cases of myeloid leukemia. In one such case, all 5-methyl-2-deoxycytidine residues have been replaced by cytidine. In a chronic lymphatic T-cell leukemia, all 5-methyl-2-deoxycytidine residues have been substituted by cytidine. In normal B lymphocytes, in two cases of chronic lymphatic B-cell leukemias and two cases of non-Hodgkin lymphomas, all 5-CG-3 sequences in this gene segment are devoid of methylation. In the TNF-beta gene, DNA methylation is
Tnfrsf1a (untagged) - Mouse tumor necrosis factor receptor superfamily, member 1a (cDNA clone MGC:6117 IMAGE:3585060), (10ug), 10 µg.
Patients with chronic low back pain (cLBP) have high rates of comorbid psychiatric disorders, mainly depression. Recent evidence suggests that depressive symptoms and pain, as interacting factors, have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Our previous work showed a higher serum level of an inflammatory marker tumour necrosis factor-alpha (TNFα) in patients with cLBP, which did not correlate with intensity of low back pain alone. In the present study we investigated the cross-sectional associations of depressive symptoms, low back pain and their interaction with circulating levels of TNFα. Each group of 29 patients with cLBP alone or with both cLBP and depression was age-matched and sex-matched with 29 healthy controls. All subjects underwent a blood draw for the assessment of serum TNFα and completed a standardised questionnaire regarding medication, depression scores according to the German version of Centre for Epidemiological Studies
Administration of sublethal doses of endotoxin (LPS) renders animals resistant to supralethal doses. This phenomenon is known as endotoxin tolerance. Macrophages from endotoxin tolerant animals exhibit reduced LPSstimulated cytokine production and arachidonic acid (AA) metabolism. Previous studies demonstrated that pertussis toxin inhibited LPS-stimulated AA metabolism in macrophages, suggesting that LPS stimulation of macrophages requires the activation of Cui proteins. Additionally, the reduced AA metabolism in tolerant macrophages is temporally correlated with reduced membrane GTPase activity and GTPyS binding. Collectively, these observations suggest the possibility that LPS tolerance leads to reduced macrophage membrane Gui protein content and that this reduction contributes to the development of LPS tolerance. Pretreatment of rats with sublethal doses of LPS or human recombinant tumor necrosis factor-a (TNFa) rendered them resistant to supralethal doses of endotoxin. Macrophages from ...
tumor necrosis factor alpha. Genetics[edit]. It is typically believed that lupus is influenced by multiple genes. Lupus is ... The influence of sex chromosomes and environmental factors are also noteworthy. Usually, these factors contribute to lupus by ... and Traditional Risk Factors". Scientific Reports. 6: 20303. Bibcode:2016NatSR...620303A. doi:10.1038/srep20303. PMC 4740809. ...
... tumor necrosis factor alpha). AGEP: Key elements promoting tissue injury in AGEP are: neutrophils; recruiters and activators of ... None-genetic ADME factors are also associated with increased risks of developing SCARs. For example, allopurinol is metabolized ... Currently, it is suspected that the expression of particular HLA proteins and T-cell receptors interact with ADME factors to ... While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in the ...
Tumor necrosis factor alpha and Interferon gamma). Induction of the high-output iNOS usually occurs in an oxidative environment ... It is synthesized by many cell types in response to cytokines and is an important factor in the response of the body to attack ... These properties may define the roles of iNOS in host immunity, enabling its participation in anti-microbial and anti-tumor ... NO produced by eNOS has been shown to be a vasodilator identical to the endothelium-derived relaxing factor produced in ...
Cleaves Pro-Leu-Ala-Gln-Ala-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNFalpha). ... ADAM 17 endopeptidase (EC, tumor necrosis factor alpha-converting enzyme, TACE) is an enzyme. This enzyme catalyses ... Black RA (January 2002). "Tumor necrosis factor-alpha converting enzyme". The International Journal of Biochemistry & Cell ...
"Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF ... ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha (TNF-α) at the surface of the cell, and ... Zheng Y, Schlondorff J, Blobel CP (November 2002). "Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE ... Black RA (January 2002). "Tumor necrosis factor-alpha converting enzyme". The International Journal of Biochemistry & Cell ...
... gene are associated with basal and tumor necrosis factor-alpha-induced transcription in monocytes". European Journal of ... "Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha-induced apoptosis. Evidence for an alternate ... as PAI-2 may have tumor-promoting and tumor-inhibiting effects. Notably, it is high expression of PAI-2 by tumor cells, not the ... Like other serpins, PAI-2 has three beta sheets (A, B, C) and nine alpha helices (hA-hI).[6][7] The structure of PAI-2 mutants ...
In humans and rabbits, tumor-necrosis factor alpha converting enzyme (T.A.C.E.) is postulated to play a significant role in the ... the tumour necrosis factor-alpha-converting enzyme (TACE)". The Biochemical Journal. 377 (Pt 2): 379-84. doi:10.1042/BJ20031321 ... "A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells". Nature. 385 (6618): 729-33. doi:10.1038 ... In GH, two disulfide bridges link four alpha-helices, and these helices make direct contact with the extracellular domain of ...
Callejas-Rubio JL, López-Pérez L, Ortego-Centeno N (December 2008). "Tumor necrosis factor-alpha inhibitor treatment for ... Cathcart S, Sami N, Elewski B (May 2012). "Sarcoidosis as an adverse effect of tumor necrosis factor inhibitors". Journal of ... and anti-tumor necrosis factor treatment (such as infliximab, etanercept, golimumab, and adalimumab). In a clinical trial ... "Relationship between tumor necrosis factor-α (TNFA) gene polymorphisms and cardiac sarcoidosis". In Vivo. 28 (6): 1125-9. PMID ...
"GCF2/LRRFIP1 represses tumor necrosis factor alpha expression". Mol Cell Biol. 25 (20): 9073-81. doi:10.1128/MCB.25.20.9073- ... "GC factor 2 represses platelet-derived growth factor A-chain gene transcription and is itself induced by arterial injury". Circ ... "Molecular cloning and characterization of a transcription regulator with homology to GC-binding factor". J Biol Chem. 273 (34 ...
Tumor necrosis factor-alpha (TNFα) is a cytokine produced by lymphocytes and macrophages, two types of white blood cells. It ... a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer". Journal of Clinical Oncology. 23 (25): 5950-59. doi: ... which is a receptor that binds to tumor necrosis factor-alpha. Second, they isolated the DNA sequence that codes the human gene ... "A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity". The Journal ...
It has been speculated that tumor necrosis factor-alpha (TNFα) might regulate the function of PDE2 in endothelial cells and ... "Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability". Blood. 105 (9 ... anti-tumour and anti-arrhythmic effects.[11] Although EHNA potently inhibits adenosine deaminase, it has been successfully used ...
Lysiak JJ (2004). "The role of tumor necrosis factor-alpha and interleukin-1 in the mammalian testis and their involvement in ... Hutson JC (1993). "Secretion of tumor necrosis factor alpha by testicular macrophages". Journal of Reproductive Immunology. 23 ... Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and ... Other immune factors found in the testis include the enzyme inducible nitric oxide synthase (iNOS), and its product nitric ...
... including tumor necrosis factor alpha, interleukin-6 and interleukin-8.[4][5] ... "Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha". The New England ... December 1998). "Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever". Nat. Med. 4 (12 ... "The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever" ...
Thalidomide was discovered to inhibit tumour necrosis factor-alpha (TNF-α) in 1991. TNF-α is a cytokine produced by macrophages ... a Potent and Orally Active Phosphodiesterase 4 and Tumor Necrosis Factor-α Inhibitor". Journal of Medicinal Chemistry. 52 (6): ... "Structural Modifications of Thalidomide Produce Analogs with Enhanced Tumor Necrosis Factor Inhibitory Activity". Journal of ... In vivo anti-tumor activity of thalidomide is believed to be due to the potent anti-angiogenic effect and also through changes ...
Tumor necrosis factor, alpha-induced protein 8 is a protein that in humans is encoded by the TNFAIP8 gene. It is preferentially ... "Entrez Gene: TNFAIP8 tumor necrosis factor, alpha-induced protein 8". Li T, Wang W, et al. (May 2018). "Genome-wide analysis ... Kumar D, Whiteside TL, Kasid U (Feb 2000). "Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, ... "Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions ...
Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the TNFAIP3 gene. This gene was ... "Entrez Gene: TNFAIP3 tumor necrosis factor, alpha-induced protein 3". Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, ... 1990). "Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific ... Opipari AW Jr; Boguski MS; Dixit VM (October 1990). "The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type ...
Corti, A; Fassina, G; Marcucci, F; Barbanti, E; Cassani, G (1992). "Oligomeric tumour necrosis factor alpha slowly converts ... "Mechanism of suramin-induced deoligomerization of tumor necrosis factor .alpha". Biochemistry. 34 (19): 6344-50. doi:10.1021/ ... Hlodan, Roman; Pain, Roger H. (1995). "The Folding and Assembly Pathway of Tumour Necrosis Factor TNFalpha, a Globular Trimeric ... Schulz, Ju¨Rgen; Sparmann, Gisela; Hofmann, Eberhard (1975). "Alanine-mediated reversible inactivation of tumour pyruvate ...
"Entrez Gene: TNFAIP6 tumor necrosis factor, alpha-induced protein 6". Mittal M, Tiruppathi C, Nepal S, Zhao YY, Grzych D, Soni ... tumor necrosis factor, alpha-induced protein 6) gene. TSG-6 is a 30 kDa secreted protein that contains a hyaluronan-binding ... "NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1". ... Tumor necrosis factor-inducible gene 6 protein also known as TNF-stimulated gene 6 protein or TSG-6 is a protein that in humans ...
"Tumor necrosis factor-alpha and interferon-gamma polymorphisms contribute to susceptibility to oral lichen planus". The Journal ... Activated CD8+ T cells induce keratinocyte apoptosis through various mechanisms such as secretion of tumor necrosis factor (TNF ... A separate study performed in China[51] found an association between a polymorphism in the TNF-alpha gene and risk for oral LP ... McCartan BE (July 1995). "Psychological factors associated with oral lichen planus". Journal of Oral Pathology & Medicine. 24 ( ...
Gupta S (2002). "Tumor necrosis factor-alpha-induced apoptosis in T cells from aged humans: a role of TNFR-I and downstream ... "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. 276 ( ... response to tumor necrosis factor. • B cell activation. • cell surface receptor signaling pathway. • response to ... tumor necrosis factor receptor binding. • cysteine-type endopeptidase activity. • hydrolase activity. • ubiquitin protein ...
Schleef RR, Chuang TL (August 2000). "Protease inhibitor 10 inhibits tumor necrosis factor alpha -induced cell death. Evidence ... Serpins are characterized by a well-conserved tertiary structure that consists of 3 beta sheets and 8 or 9 alpha helices. A ... "Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins". Biochemistry. 28 ...
"Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia". Journal of Neurochemistry. 75 (3): 965-72. ... "Activation of P2X7 receptors induces CCL3 production in microglial cells through transcription factor NFAT". Journal of ...
"Entrez Gene: TNFAIP1 tumor necrosis factor, alpha-induced protein 1 (endothelial)". Wolf FW, Marks RM, Sarma V, et al. (1992 ... This gene was identified as a gene whose expression can be induced by the tumor necrosis factor alpha (TNF) in umbilical vein ... "Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific ... "Characterization of a novel tumor necrosis factor-alpha-induced endothelial primary response gene". J. Biol. Chem. 267 (2): ...
Boland A, Cornelis GR (1998). "Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during ... Correlation with its inhibitory effect on tumor necrosis factor-alpha production". J. Biol. Chem. 272 (25): 15920-7. doi: ... Structurally, it is unlike any other superantigen, but is remarkably similar to the tumour necrosis factor and viral capsid ... Since this pathway gives secretion selectivity, it is a virulence factor. In contrast to the ysc and yop genes listed above, ...
Carballo E, Lai WS, Blackshear PJ (August 1998). "Feedback inhibition of macrophage tumor necrosis factor-alpha production by ... It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2. TTP binds to AU-rich ... DuBois RN, McLane MW, Ryder K, Lau LF, Nathans D (Dec 1990). "A growth factor-inducible nuclear protein with a novel cysteine/ ... For example, TTP is a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its mRNA ...
"Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia". Journal of Neurochemistry. 75 (3): 965-72. ... Crosstalk between tumor cells and TAMs is characterized by the release of growth factors and cytokines by TAMs in response to ... Tumor-associated macrophages/microglia (TAMs) are the main infiltrate in gliomas, comprising up to 40% of the tumor mass. TAMs ... Not only tumor cells, but also non-tumor cells of the microenvironment contribute to cancer progression and response to ...
Davis JM, Narachi MA, Alton NK, Arakawa T (1987). "Structure of human tumor necrosis factor alpha derived from recombinant DNA ... 2000). "Integrin binding specificity of laminin-10/11: laminin-10/11 are recognized by alpha 3 beta 1, alpha 6 beta 1 and alpha ... Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are ... Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they ...
2001). "A novel tumor necrosis factor-alpha inhibitory protein, TIP-B1". Int. J. Immunopharmacol. 22 (12): 1137-42. doi:10.1016 ... reported SH3BGRPL3 protein as a post-translational modification of the 27kDa tumor necrosis factor alpha (TNF-α) inhibitory ... 1999). "Identification, characterization, and cloning of TIP-B1, a novel protein inhibitor of tumor necrosis factor-induced ... Conversely, the related protein SH3BGRL is reported to be downregulated in fibroblasts, lymphoid cells, and splenic tumor cells ...
... and tumor necrosis factor alpha in splenic Gaucher cells (engorged macrophages). Gaucher disease is suggested based on the ... Prenatal diagnosis is available and is useful when a known genetic risk factor is present. A diagnosis can also be implied by ... making this the most common known genetic risk factor for Parkinson's. Cancer risk may be increased, particularly myeloma. This ...
Shedding of the glycocalyx can be triggered by inflammatory stimuli, such as tumor necrosis factor-alpha. Whatever the stimulus ... along with many other factors, can cause damage to the delicate glycocalyx. These studies are evidence that the glycocalyx ...
These gene candidates include certain variations in tumor necrosis factor-alpha (TNF-alpha), IL-1 alpha, and CYP1A1 genes, ... High levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are also associated with worsened acne.[42] Both ... Risk factors for the development of acne, other than genetics, have not been conclusively identified. Possible secondary ... These include alpha hydroxy acid, anti-androgen medications, antibiotics, antiseborrheic medications, azelaic acid, benzoyl ...
... and their antagonists regulate spontaneous and tumor necrosis factor (TNF)-induced proinflammatory cytokine and chemokine ... Koon HW, Zhao D, Na X, Moyer MP, Pothoulakis C (Oct 2004). "Metalloproteinases and transforming growth factor-alpha mediate ... Azzolina A, Bongiovanni A, Lampiasi N (Dec 2003). "Substance P induces TNF-alpha and IL-6 production through NF kappa B in ... the role of brain-derived neurotrophic factor and substance P". The British Journal of Dermatology. 157 (5): 922-5. doi:10.1111 ...
June 2004). "Genetic polymorphisms in tumor necrosis factor (TNF)-alpha and TNF-beta in a population-based study of systemic ... Most important of which is the TNF (tumor necrosis factors) with 3 loci in the region. Starting from B8, immediately followed ... 1993). "Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus: TNFB-MHC haplotypes". ... There are many genes that lie on either side of HLA-B, TNF alpha is over expressed. Closer to DR3, C4A is null in B8-DR3 ...
Fukuoka M, Yasuda K, Fujiwara H, Kanzaki H, Mori T. Interactions between interferon gamma, tumour necrosis factor alpha, and ... 風險因子(英语:Risk factor). 肥胖症、運動不足、家族病史[8]. ... 2-Hour oral glucose tolerance test (GTT) in women with risk factors (obesity, family history, history of gestational diabetes)[ ... Kelly CJ, Stenton SR, Lashen H. Insulin-like growth factor binding protein-1 in PCOS: a systematic review and meta-analysis. ...
... activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. UNITED ... activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. 272 (5): ... 1997). "Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor". Cancer Res. 57 (19): 4177-82. PMID ... 1998). "Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene ...
... tumor necrosis factor (TNF) ... alpha interferon (INFa) - alternative medicine - alveolar - ... granulocyte macrophage-colony stimulating factor (GM-CSF) - granulocyte-colony stimulating factor (G-CSF) - granulocytopenia ... host factors - HPTN - HPV - HRSA - HTLV-I - HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) - HTLV-II - ...
... has been shown to enhance apoptosis caused by chemotherapeutic drugs through autocrine-secreted tumor necrosis factor alpha ( ... One approach used by tumors to upregulate growth and survival is through autocrine production of growth and survival factors. ... causing tumor recurrence. For example, despite widespread expression of epidermal growth factor receptors (EGFRs) and EGF ... Another group found that high serum levels of IL-6 correlated with poor outcome in breast cancer tumors. Their research showed ...
"Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an ... 2003). "Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 ... 2000). "Permissive factors for HIV-1 infection of macrophages". J. Leukoc. Biol. 68 (3): 303-10. PMID 10985244. CS1 održavanje ... Köhidai L, Csaba G (July 1998). "Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF-alpha) in ...
tumor necrosis factor-activated receptor activity. • nerve growth factor binding. Cellular component. • cytoplasm. • integral ... Interferon alpha (interferon alfa, IFN-α). *Interferon alfa (IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, ... CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker. ... "Entrez Gene: TNFRSF8 tumor necrosis factor receptor superfamily, member 8".. *^ Teng LH, Lu DH, Xu QZ, Fu YJ, Yang H, He ZL ( ...
There is evidence that emphasizes the role of autophagy both as a tumor suppressor as well as a factor in tumor cell survival. ... Necrosis and chronic inflammation also has been shown to be limited through autophagy which helps protect against the formation ... Parkinson's disease is characterized by inclusions of a protein called alpha-synuclien (Lewy bodies) in affected neurons that ... Tumor cell survival[edit]. Alternatively, autophagy has also been shown to play a huge role in tumor cell survival. In ...
TNF, DIF, TNF-alpha, TNFA, TNFSF2, Tumour necrosis factor, TNF-α, tumor necrosis factor, TNLG1F, Tumor necrosis factor alpha. ... Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα, cachexin, or cachectin) is a cell signaling protein (cytokine) ... reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF).[14] Both factors were ... Tumor+Necrosis+Factor-alpha at the US National Library of Medicine Medical Subject Headings (MeSH) ...
Neurons of PD patients show hypomethylation of tumor necrosis factor (TNF) alpha encoding sequence, overexpression of which ... In an alpha-synuclein overexpressing Drosophila model of PD, vorinostat (as well as sodium butyrate) reduced alpha-synuclein- ... a neurotrophic factor important for long-term memory.[66] Expression of CREB, an activity-dependent transcription factor ... IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and ...
"Tumor necrosis factor-alpha is involved in thrombolytic-induced hemorrhage following embolic strokes in rabbits". Department of ... "Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic ... Tumor juga ditemukan di permukaan non-valvular, seperti di bilik kiri. Ukuran tumor bervariasi dari 2 mm hingga 70 mm.[46] ... "Stroke risk factors and stroke prevention". Department of Neurology, College of Physicians and Surgeons, Columbia University; ...
"Five tumor necrosis factor-inducible cell adhesion mechanisms on the surface of mouse endothelioma cells mediate the binding of ... platelet alpha granule membrane. • platelet dense granule membrane. • external side of plasma membrane. • extracellular space. ... increased levels of P-selectin mRNA and protein are induced by inflammatory mediators such as tumor necrosis factor-a (TNF-a), ... Its activity in tumor metastasis has been probed by the addition of heparin that functions to blocks tumor metastasis. In ...
Mutlu, G., Mutlu, E., Bellmeyer, A., Rubinstein, I. Pulmonary adverse events of anti-tumor necrosis factor-alpha antibody ... Strachan, D. P., Powell, K. J., Thaker, A., Millard, F. J., Maxwell, J. D. Vegetarian diet as a risk factor for tuberculosis in ... Kallmann, F. J., Reisner, D. Twin studies on the significance of genetic factors in tuberculosis. American Review of ...
In vitro data also suggest that activated protein C may exert an anti-inflammatory effect by inhibiting tumor necrosis factor ... Drotrecogin alpha (activated) belongs to the class of serine proteases. Drotrecogin alfa has not been found to improve outcomes ... Factor Xa inhibitors. (with some II inhibition). Heparin group/. glycosaminoglycans/. (bind antithrombin). *Low molecular ... In vitro data suggest that activated protein C exerts an antithrombotic effect by inhibiting factors Va and VIIIa, and that it ...
Heparin-binding EGF-like growth factor (HB-EGF). *Murodermin. *Nepidermin. *Transforming growth factor alpha (TGFα) ... Tumor necrosis factor. *Wnt protein. see also extracellular ligand disorders. *v. *t ...
Tumor necrosis factor alpha. Receptor. *Tumor necrosis factor receptor 1. *Tumor necrosis factor receptor 2 ... Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor-1 (Apaf-1).[5] ... Kroemer G, Dallaporta B, Resche-Rigon M (1998). "The mitochondrial death/life regulator in apoptosis and necrosis". Annual ...
... transactivates the epidermal growth factor receptor through specific E-prostanoid receptors and tumor necrosis factor-alpha ... tumor necrosis factor α (TNF-α), tumor necrosis factor β (TNF-β), transforming growth factor α (TGF-α),[67] transforming growth ... "Expression of the transforming growth factor-alpha/epidermal growth factor receptor pathway in normal human breast epithelial ... factor β (TGF-β),[68] heregulin,[69] Wnt,[40] RANKL,[40] and leukemia inhibitory factor (LIF).[40] These factors regulate ...
Rudloff HE, Schmalstieg FC, Mushtaha AA, Palkowetz KH, Liu SK, Goldman AS (January 1992). "Tumor necrosis factor-alpha in human ... tumor necrosis factor,[22] chemokines,[23] and others. Colostrum also contains a number of growth factors, such as insulin-like ... transforming growth factors alpha,[26] beta 1 and beta 2,[27][28] fibroblast growth factors,[29] epidermal growth factor,[30] ... platelet-derived growth factor,[31] vascular endothelial growth factor,[32] and colony-stimulating factor-1.[33] ...
Patients in the early stage of disease showed a decrease in coagulation factors (e.g. platelets, prothrombin, and globulin) and ... most often the result of postvaccinial encephalitis or severe necrosis in the area of vaccination (called progressive vaccinia ... Alpha. .mw-parser-output .nobold{font-weight:normal}. HSV. *Herpes simplex. *Herpetic whitlow ... Such disruption and population losses were an important factor in the Spanish achieving conquest of the Aztecs and the Incas.[ ...
Induction of tumor necrosis factor and cytotoxicity by macrophages exposed to lactoperoxidase and microperoxidase. . In: Life ... The metabolism of 17 alpha-estradiol by lactoperoxidase: a possible source of oxidative stress in breast cancer. . In: ...
Tumor Necrosis Factor-alpha Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA. ... Tumor necrosis factor (TNF) alpha increases collagen accuulation and proliferation in intestinal myofibrobasts via TNF Recptor ... "Tumour necrosis factor alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel ... "A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells". Nature 385 (6618): 729-33. Bibcode: ...
Cytokines such as tumor necrosis factor, interleukin 1, and interleukin 6 may activate procoagulation factors in the cells ... Recombinant activated protein C (drotrecogin alpha) was originally introduced for severe sepsis (as identified by a high APACHE ... Microbial factors[edit]. Bacterial virulence factors, such as glycocalyx and various adhesins, allow colonization, immune ... Consequentially, transcription factors such as nuclear factor-kappa B and activator protein-1, will up-regulate the expression ...
N. Konuk, I. O. Tekın, U. Ozturk u. a.: Plasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive ... N. Konuk, I. O. Tekın, U. Ozturk u. a.: Plasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive ... pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α ... T. K. Murphy, E. A. Storch, A. B. Lewin, P. J. Edge, W. K. Goodman: Clinical factors associated with pediatric autoimmune ...
Correlation with its inhibitory effect on tumor necrosis factor-alpha production". J. Biol. Chem. 272 (25): 15920-7. PMID ... "Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during Yersinia infection". Infect. Immun. 66 ... Estruturalmente, é diferente a calquera outro superantíxeno, mais é moi similar ao factor de necrose tumoral e a proteínas de ... Brubaker RR (1983). "The Vwa+ virulence factor of yersiniae: the molecular basis of the attendant nutritional requirement for ...
The inflammatory mediators are: Interleukin 1 beta, Interleukin 6, Tumor necrosis factor alpha (TNF alpha), MMP1, MMP2, MMP9, ... Risk factors[edit]. Intracranial aneurysms may result from diseases acquired during life, or from genetic conditions. Lifestyle ... The most significant factors in determining outcome are the Hunt and Hess grade, and age. Generally patients with Hunt and Hess ... Coarctation of the aorta is also a known risk factor,[5] as is arteriovenous malformation.[7] Genetic conditions associated ...
... such as tumor necrosis factor-alpha (TNFα), interleukins 1 and 6 and corticotropin-releasing hormone (CRH) influence appetite ... Physiological factors[edit]. There is no neurological explanation as to why chocolate fudge cake evokes more appetite than ... Both genetic and environmental factors may regulate appetite, and abnormalities in either may lead to abnormal appetite. Poor ... factors. Likewise, hyperphagia (excessive eating) may be a result of hormonal imbalances, mental disorders (e.g., depression) ...
"Tumor Necrosis Factor-alpha". Drug Information Portal. U.S. National Library of Medicine. Tumor Necrosis Factor-alpha at the US ... Tumor necrosis factor (TNF, cachexin, or cachectin; often called tumor necrosis factor alpha or TNF-α) is a cytokine - a small ... Ghada A. Abd El Latif, Tumor necrosis factor alpha and keratin 17 expression in oral submucous fibrosis in rat model, E.D.J. ... reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF). Both factors were described ...
... tumor necrosis factor alpha). AGEP: Key elements promoting tissue injury in AGEP are: neutrophils; recruiters and activators of ... None-genetic ADME factors are also associated with increased risks of developing SCARs. For example, allopurinol is metabolized ... Currently, it is suspected that the expression of particular HLA proteins and T-cell receptors interact with ADME factors to ... While these viral reactivations, particularly of human herpes virus 6, have been suggested to be an important factor in the ...
Ribosome Binding Factor A (RBFA) * Tumor Necrosis Factor alpha (TNF) * S-Adenosyl-Methionine Synthase (METK) ... Ankyrin Repeat and Sterile alpha Motif Domain Containing 1B Proteine * Ankyrin Repeat and Sterile alpha Motif Domain Containing ... Hemoglobin, alpha 1 (HBA1) * serpin Peptidase Inhibitor, Clade E (Nexin, Plasminogen Activator Inhibitor Type 1), Member 1 ( ...
Tumor Necrosis Factor alpha (TNF) * Interleukin 1, beta (IL1B) * Tumor Protein P53 (TP53) ... The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. ... Catenin (Cadherin-Associated Protein), alpha 1, 102kDa ELISA Kits * Catechol-O-Methyltransferase Domain Containing 1 ELISA Kits ...
ALSO: Gq/11 activates MAPK, which in turn regulates TNF-alpha.. "Among the MAPKs, p38 MAPK regulates the expression of tumor ... Tumor Necrosis Factor (TNF-α). ©2020 PFPC. COVID-19. "Early reports have demonstrated severely elevated levels of inflammatory ... Tumor Necrosis Factor (TNF-α). A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid ... tumor necrosis factor (TNF)-α, interleukin (IL)-2R and ferritin (112)." (Atri et al., 2020; Qin et al., 2020). Qin C, Zhou L, ...
PubMed:[Effect of acetyl-L-carnitine on the insulin resistance of L6 cells induced by tumor necrosis factor-alpha].. ... PubMed:Acetyl-l-carnitine inhibits TNF-alpha-induced insulin resistance via AMPK pathway in rat skeletal muscle cells.. ... PubMed:L-Carnitine changes the levels of insulin-like growth factors (IGFs) and IGF binding proteins in streptozotocin-induced ... PubMed:Factors affecting the distribution of ingested propionic acid in the rat forestomach.. ...
The comparative one-year performance of anti-tumor necrosis factor alpha drugs in patients with rheumatoid arthritis, psoriatic ... Tumour necrosis factor inhibitor monotherapy vs combination with MTX in the treatment of PSA: a systematic review of the ... Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor ... targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin ...
Adalimumab is a tumor necrosis factor-alpha (TNF-α) inhibitor that patients can self-administer at home after receiving proper ...
Erelzi belongs to a group of drugs called tumor necrosis factor-alpha inhibitors. These work by blocking the action of a ...
These medications work by blocking tumor necrosis factors (TNFs), factors partly responsible for over-inflammation in certain ... Tumor necrosis factor alpha. Side Effects of Golimumab. Back to Top. Serious side effects have been reported with golimumab. ...
Inflectra belongs to a group of drugs called tumor necrosis factor-alpha inhibitors. These work by blocking the action of a ... have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab ...
... tumor necrosis factor-alpha receptor-associated factor 6, a diverging point in the Toll-like receptor 9-signaling. Yeo, S.J., ... tumor necrosis factor-alpha receptor-associated factor 6, a diverging point in the Toll-like receptor 9-signaling.. The immune ... Myeloid differentiation factor 88-dependent post-transcriptional regulation of cyclooxygenase-2 expression by CpG DNA: ... Myeloid differentiation factor 88-dependent post-transcriptional regulation of cyclooxygenase-2 expression by CpG DNA: ...
... or are unable to tolerate conventional CD therapies and inhibitors of tumor necrosis factor-alpha (TNF-a). Natalizumab should ... In May 2015, new risk factor for progressive multifocal leukoencephalopathy is added to drug safety labelling.References. ...
Potential therapeutic targets, such as blockade of the B cell-activating factor, the role of interferon-alpha, and targeting ... The last of these includes what has been learned from trials blocking tumor necrosis factor and, more recently, anti-CD20 ... and tumor necrosis factor-alpha (TNF-α) in the context of the local production in the inflamed salivary tissues. ... The last of these includes what has been learned from trials blocking tumor necrosis factor and, more recently, anti-CD20 ...
Tumor necrosis factor alpha (TNFA) exists in two biologically active forms, a transmembrane TNF-alpha (tmTNFA) and secretory ... The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor ... Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in experimental cerebral malaria Lucas, R, ... Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B or hereafter referred as TNFR2) preferentially binds with ...
Tumor Necrosis Factor-Alpha, Body Fluid or CSF. Sunquest Code:. TNF1AN. Epic Code:. LAB6630. Epic Name:. Tumor Necrosis Factor ... Cytokines; TNFa; TNF-Alpha; Tumor Necrosis Factor Alpha. Methodology:. Enzyme linked immunosorbent assay. ...
TNF Cake - Tastier than Tumor Necrosis Factor Alpha. *. April 24, 2016. April 25, 2016. ... You see, it is not too often that we go out on Saturday morning and run into… Read More »TNF Cake - Tastier than Tumor Necrosis ...
α-Tocopherol, but Not γ-Tocopherol, Attenuates the Expression of Selective Tumor Necrosis Factor-Alpha-Induced Genes in Primary ... Zolpidem activation of alpha 1-containing GABAA receptors selectively inhibits high frequency action potential firing of ...
Tumor Necrosis Factor-alpha 8% * Calcium 7% * Apoptosis 7% * Data storage equipment 6% ...
They included patients who were naïve to tumour necrosis factor alpha antagonist (anti-TNF-α) therapy and patients who had an ...
... tumor necrosis factor alpha). Astaxanthin as a Skin Health Supplement. One of the reasons why salmon roe is red in color has to ...
... review considers the pharmacological management of rheumatoid arthritis including the role of anti-tumour necrosis factor alpha ... review considers the pharmacological management of rheumatoid arthritis including the role of anti-tumour necrosis factor alpha ... review considers the pharmacological management of rheumatoid arthritis including the role of anti-tumour necrosis factor alpha ... review considers the pharmacological management of rheumatoid arthritis including the role of anti-tumour necrosis factor alpha ...
While studying potential treatments for sepsis-particularly to target tumor necrosis factor (TNF), Vilcek and Junming Le ... created a monoclonal antibody against TNF-alpha, called infliximab. The chimeric antibody was ineffective in treating sepsis- ...
... reduce Tumor Necrosis Factor alpha - BRCA2 - arthritis/RA/Sjogrens - dont sweat during exercise - rosacea. Location:. Princeton ...
Biomarker for efficient prediction and monitoring of tumor necrosis factor alpha in inflammation inhibition therapies. A German ...
... transforming growth factor beta; tumor necrosis factor-alpha. Abstract:. ... The main purpose of this study was to evaluate the ... 1. Identification of regulatory factors promoting embryogenic callus formation in barley through transcriptome analysis ... 3. Manipulating a Single Transcription Factor, Ant1, Promotes Anthocyanin Accumulation in Barley Grains ... For studying developmental genes in the xylem of this species, we investigated the Myb transcription factor family, one of the ...
Mice, Inbred BALB C; Tumor Necrosis Factor-alpha; Virus Activation. 1997. 10. Digre, Kathleen B.; Gouw, Launce G.; Harris, ... Hemifacial spasms; Tumors; Dolichoectiatic vertebrobasilar artery. 1988-07. 17. Baehr, Wolfgang. Calcium-sensitive particulate ... The primary tumors that typically cause carcinomatous meningitis include lung cancer, breast cancer, leukemia, lymphoma and ... Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human ...
Tumor Necrosis Factor Alpha. September 24, 2019. Next post. Top Ten CPAP Masks. September 24, 2019 ...
... tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were stored at − 80 °C then all samples were analyzed together. ... tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and, stored at − 80 °C until the completion of the study and all ... tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were stored at − 80 °C then all samples were analyzed together. ... First, mobility limitation is known to be a risk factor for worse postoperative outcomes; our prospective cohort study ...
Tumor Necrosis Factor alpha (TNF) * V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT1) ... anti-Protein Kinase, CAMP-Dependent, Regulatory, Type II, alpha Anticorps * anti-Protein Phosphatase 1, Regulatory (Inhibitor) ... anti-Protein Phosphatase 1, Catalytic Subunit, alpha Isoform Anticorps * anti-Protein O-Linked Mannose Beta1,2-N- ...
  • The Effect of Anti-Tumor Necrosis Factor-Alpha Treatment on Muscle Performance and Endurance in Patients With Ankylosing Spondylitis: A Prospective Follow-Up Study. (
  • Although the mechanism of muscle loss is not clear, it has been thought that anti-tumor necrosis factor-alpha (anti-TNF-[alpha]) causes muscle loss by stimulating muscle protein destruction and inhibiting myogenic differentiation. (
  • Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). (
  • Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist. (
  • Rat colon was exposed to tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) in Ussing chambers. (
  • INDEPENDENT VARIABLES: Serum concentration of tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), basic fibroblast growth factor (bFGF), platelet derived growth factor BB (PDGF-BB), interferon gamma (IFN-γ), and vascular-derived endothelial growth factor (VEGF) were the independent variables. (
  • 1993 ). Modulation of human endothelial cell permeability by combinations of the cytokines interleukin-1 alpha/beta, tumor necrosis factor-alpha and interferon-gamma. (
  • Interleukin 12, interferon gamma, and tumor necrosis factor alpha are the key cytokines of the generalized Shwartzman reaction. (
  • The binding of TNF to its receptor and its displacement by LT confirmed the functional homology between the two factors. (
  • Polymorphism of the tumor necrosis factor-alpha receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet-treated type 2 diabetic patients. (
  • OBJECTIVE: Mice lacking the tumor necrosis factor-alpha receptor 2 (TNFR2) gene fed a high-fat diet gain less weight and display reduced leptin and insulin levels. (
  • Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor. (
  • The presence of a MO alpha-adrenergic receptor was established by demonstrating binding of the alpha 2-adrenergic antagonist 3H-yohimbine to membranes prepared from MO. (
  • Tumor necrosis factor-alpha acutely inhibits insulin signaling in human adipocytes: implication of the p80 tumor necrosis factor receptor. (
  • Interaction of TNF-alpha with insulin signaling was determined by quantification of insulin receptor substrate (IRS)-1-associated PI 3-kinase activity. (
  • The inhibitory action of TNF-alpha was dose-dependent, already detectable at 10 pmol/l, and was correlated to inhibition of tyrosine phosphorylation of IRS-1 with an unaltered autophosphorylation of the insulin receptor beta-subunit. (
  • Possible mechanisms might include a direct effect of TNF-alpha on phospholipid secretion and/or reuptake, or an indirect effect via alteration of the type II pneumocytes' response to beta-adrenergic receptor stimulation. (
  • a soluble receptor and a TNF-alpha-converting enzyme inhibitor are other possibilities. (
  • Brambilla F, Monti D, Franceschi C. Plasma concentrations of interleukin-1-beta, interleukin-6 and tumor necrosis factor-alpha, and of their soluble receptors and receptor antagonist in anorexia nervosa. (
  • degenerative and regenerative roles of tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine with pleiotropic functions, were investigated by using TNF receptor 1 and 2 double knockout (TNFR-DKO) and TNF-alpha antibody neutralized mice following traumatic freeze injury to the tibialis anterior muscle. (
  • 1990 ). Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity. (
  • In the present study, we extended this previous observation by comparing the effect of Tg and other calcium-mobilizing G-protein-coupled receptor (GPCR) agonists on the expression of different pro-inflammatory genes in response to tumor necrosis factor (TNF)-alpha in ASM cells. (
  • We found that both protein and messenger RNA expression of cyclooxygenase-2, prostaglandin E2, prostanoid receptor-1, tumour necrosis factor-α and interleukin-1β were consistently higher in the forebrain of pups with intraventricular haemorrhage relative to pups without intraventricular haemorrhage. (
  • Cyclooxygenase-2, prostanoid receptor-1 or tumour necrosis factor-α inhibition reduced inflammatory cell infiltration, apoptosis, neuronal degeneration and gliosis around the ventricles of pups with intraventricular haemorrhage. (
  • Cyclooxygenase-2 or prostanoid receptor-1 inhibition reduced tumour necrosis factor-α level, but not interleukin-1β. (
  • Hence, prostanoid receptor-1 and tumour necrosis factor-α are downstream to cyclooxygenase-2 in the inflammatory cascade induced by intraventricular haemorrhage, and cyclooxygenase-2-inhibition or suppression of downstream molecules - prostanoid receptor-1 or tumour necrosis factor-α- might be a viable neuroprotective strategy for minimizing brain damage in premature infants with intraventricular haemorrhage. (
  • In the first part of this thesis we examined the possibilities of using the cytokine tumor necrosis factor-alpha (TNFcx) for the latter aproach. (
  • 5 ]. While studying the actions of the atherorelevant cytokine tumor necrosis factor alpha (TNFα) on macrophage survival and apoptosis, we recently showed for the first time that in human, THP-1-derived macrophages (TDMs), as in other cell types, Ca 2+ influx is also critical to support survival signaling [ 6 ]. (
  • We investigated the anti-inflammatory potentials of a safe, common dietary flavonoid component, quercetin, for its ability to modulate the production and gene expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) by human peripheral blood mononuclear cells (PBMC). (
  • Tumor necrosis factor ( TNF , tumor necrosis factor alpha , TNFα , cachexin , or cachectin ) is a cell signaling protein ( cytokine ) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction . (
  • See the reference protein sequence for tumor necrosis factor alpha-induced protein 3 isoform 2 (NP_001159874.1). (
  • TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. (
  • Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely low or undetectable. (
  • TNF-alpha and C-reactive protein (CRP) serum concentrations, erythrocyte sedimentation rate, and leukocyte count were measured in 26 MDD patients and in 17 controls. (
  • One such protein is tumour necrosis factor α (TNFα), a member of the immune system. (
  • These studies concerning IL-10 mRNA induction by TNF-alpha were corroborated by studies of IL-10 protein secretion: TNF-alpha alone, but not IL-1 alpha, IL-1 beta, or IL-6 induces substantial IL-10 secretion. (
  • In this report, the effects of elevated temperature and dexamethasone on LPS-stimulated IL-1 beta and TNF alpha mRNA gene expression and protein synthesis were studied in human astrocytoma cell lines and primary cultures of human fetal astrocytes. (
  • Cells cultured at 40 degrees C exhibited smaller peaks of IL-1 beta and TNF alpha transcription and protein synthesis compared with cells cultured at 37 degrees C. The addition of dexamethasone before, during, or after exposure of the cells to LPS resulted in temperature-dependent inhibition of IL-1 beta transcription and protein synthesis. (
  • Incubation of THLE-5b cells with TNF-alpha stimulated PAI-1 production via protein kinase C-, mitogen-activated protein kinase-, protein tyrosine kinase-, and nuclear factor-kappaB-dependent pathways. (
  • A thiazolidinedione, pioglitazone, reduced TNF-alpha-induced PAI-1 production by 32%, via protein kinase C- and nuclear factor-kappaB-dependent pathways. (
  • OBJECTIVES: To examine the effect of tumor necrosis factor-alpha (TNF-alpha) on pulmonary artery pressure and on total protein, phospholipid, lysophosphatidylcholine, phosphatidylcholine, phosphatidylinositol, and phosphatidylglycerol content in the bronchoalveolar lavage-accessible space of the isolated perfused rat lung, and to evaluate the role of the lung in the clearance of TNF-alpha from the perfusion medium in this model. (
  • SCA patients at steady state have chronically elevated levels of tumor necrosis factor alpha (TNF-α), interleukins (ILs) such as IL-1b, IL-6 and IL-8, C-reactive protein and soluble adhesion molecules. (
  • Human eosinophils can express the cytokines tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha. (
  • TNF-alpha protein was detectable by immunohistochemistry in blood eosinophils of hypereosinophilic subjects, and purified blood eosinophils from three atopic donors exhibited cycloheximide-inhibitable spontaneous release of TNF-alpha in vitro. (
  • Many blood eosinophils (39-91%) from hypereosinophilic donors exhibited intense labeling for macrophage inflammatory protein-1 alpha (MIP-1 alpha) mRNA, whereas eosinophils of normal donors demonstrated only weak or undetectable hybridization signals for MIP-1 alpha mRNA. (
  • Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK. (
  • This property of P58 IPK has been exploited by influenza virus, which recruits P58 IPK to repress PKR-mediated eukaryotic initiation factor 2α (eIF-2α) phosphorylation ( 32 , 33 ), thereby enabling influenza virus to evade the host antiviral response by maintaining a high level of protein synthesis. (
  • IL-1 and TNF-α signaling pathways converge more distally at the level of mitogen-activated protein kinase kinase kinases (MAP3Ks), leading ultimately to the activation of MAPKs (p38, c-Jun NH 2 -terminal kinase [JNK], and extracellular signal-regulated kinase) and the transcription factor nuclear factor-κB (NF-κB) ( 47 , 55 ). (
  • IL-8, IL-6, growth-regulated oncogene alpha [GRO-α], and monocyte chemoattractant protein 1 [MCP-1]), as well as adhesion and costimulatory molecules that recruit and activate various aspects of the innate and adaptive immune response. (
  • Treatment of cultured chondrocytes by TNF-alpha induced translocation of activated RelA to the nuclei, followed by upregulation of tenascin-C expression in both mRNA and protein. (
  • In wild-type control mice, TNF-alpha mRNA transcripts and protein increased following injury and gradually returned to control (uninjured) levels by 13 days. (
  • Mechanism of TNF-{alpha} modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression. (
  • This protein has been shown to form a stable complex with inter-alpha-inhibitor (I alpha I), and thus enhance the serine protease inhibitory activity of I alpha I, which is important in the protease network associated with inflammation. (
  • 2-Aminoethoxydiphenyl borate (APB), a blocker of store-operated calcium channels (SOCs), and bisindolylmaleimide I (Bis I), a broad-spectrum protein kinase C (PKC) inhibitor, inhibited the basal and synergic effects of IL-6 secretion in response to calcium-mobilizing agents and TNF-alpha, but did not prevent the abrogated effect of RANTES secretion. (
  • 1) TNF-alpha is synthesized as a type II membrane protein, which can be cleaved by a membrane-associated metalloproteinase. (
  • often called tumor necrosis factor alpha or TNF-α) is a cytokine - a small protein used by the immune system for cell signaling. (
  • Effect of inhibitor of tumor necrosis factor-alpha and oxatomide on immune mediated otitis media. (
  • The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin inhibited TNF-alpha-induced PAI-1 production by 59%, which was reversed by coincubation with mevalonic acid. (
  • Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor? (
  • whereas Rottlerlin, a PKC-delta inhibitor, inhibited both Thr- and TNF-alpha-induced expression of IL-6, while BK-induced IL-6 secretion was not affected. (
  • To investigate whether two new-generation anti-folate drugs, PT523 (DHFR-inhibitor) and ZD1694 (TS-inhibitor), have equal or better anti-inflammatory capacity compared with MTX based on their capacity to inhibit tumour necrosis factor alpha (TNF-α) production by activated T cells. (
  • [20] [21] More recently, research in the Laboratory of Mark Mattson has shown that TNF can prevent the death/ apoptosis of neurons by a mechanism involving activation of the transcription factor NF-kappaB which induces the expression of Mn-SOD and Bcl-2 . (
  • Rapid acceleration of neutrophil apoptosis by tumor necrosis factor-alpha. (
  • We demonstrate here that human necrosis factor-alpha, a potent neutrophil activator, induces rapid (within 3 h) apoptosis of these cells, i.e. neutrophils treated with this cytokine exhibit (i) light and electron microscopic changes characteristic to apoptotic cells, (ii) reduced propidium iodide binding to DNA, and (iii) the ladder form of DNA, as shown by agarose gel electrophoresis. (
  • In the present study, we investigated the anti-apoptotic effect of BV on tumor necrosis factor (TNF)-alpha with actinomycin (Act) D induces apoptosis in hepatocytes. (
  • A molecular model of tumour necrosis factor-alpha (TNF), a cytokine responsible for regulating immune cell activity by inducing fever, apoptosis and inflammation by binding to receptors located on cell membranes. (
  • Bilotas M, Meresman G, Buquet R, Sueldo C, Barañao RI (2010) Effect of vascular endothelial growth factor and interleukin-1 beta on apoptosis in endometrial cell cultures from patients with endometriosis and controls. (
  • In contrast, both the P58 IPK and ΔTPR6 cell lines were resistant to tumor necrosis factor alpha-induced apoptosis, suggesting that P58 IPK may function as a more general suppressor of programmed cell death independently of its PKR-inhibitory properties. (
  • NF-κB is a critical transcription factor that serves as a major modulator of inflammation, immune regulation, differentiation, and apoptosis ( 19 , 24 ). (
  • It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. (
  • Genetic factors, especially related to cytokines, may play important roles in susceptibility to pancreatic injury, as well as in the severity and evolution of the inflammatory process [ 5 ]. (
  • These studies have not focused on tumor necrosis factor-alpha as a possible marker for inflammatory damage. (
  • Over the last 15 years, an increasing body of evidence has suggested a causal relationship between depression and the immunological activation and hypersecretion of pro-inflammatory cytokines, such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha (TNF-alpha). (
  • TNF-alpha(TNF), a pro-inflammatory cytokines, is expressed in ischemic tissues and is known to modulate angiogenesis. (
  • 2 The elevated inflammatory factors would not only influence the initial establishment of osseointegration but also the long-term maintenance. (
  • The most validated inflammatory cytokine is the tumor necrosis factor alpha (TNF-α), which is involved in the focal loss of cartilage in osteoarthritis. (
  • ROS also modulate a number of cell signaling pathways resulting in transcription factor activation and inflammatory mediators' release [ 4 ]. (
  • Furthermore, LPS induces a large amount of IL-10 secretion that is largely inhibited (50 to 75%) by anti-TNF-alpha but not by antibodies to other inflammatory cytokines. (
  • Taken together, these findings suggest that TNF-alpha is unique among the inflammatory cytokines in its role as an inducer of IL-10 in human monocytes, as such, it induces a molecule that provides negative feedback to its own production. (
  • These investigations support the role of alpha 2 adrenergic agonists as immunostaining compounds that may regulate cytokine production during an inflammatory response. (
  • All members of the TNF superfamily, without exception, have an inflammatory role, in part, through activation of the transcription factor, nuclear factor kappa B (NF-kB). (
  • These antibodies are potent tumor necrosis factor (TNF) inhibitors and efficient therapeutics for many inflammatory diseases. (
  • Viral infection is associated with a vigorous inflammatory response characterized by cellular infiltration and release of the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α). (
  • Glucocorticoids (GCs) and anti-tumor necrosis factor-α (anti-TNF-α) agents are used for treatment of inflammatory bowel diseases (IBD) and juvenile idiopathic arthritis (JIA). (
  • These results show that calcium-mobilizing GPCR agonists functionally interact with TNF-alpha to differentially regulate pro-inflammatory genes expression in human ASM cells, possibly by involving Tg-sensitive intracellular calcium stores, SOC and PKC. (
  • Tumor necrosis factor (TNF) is an important inflammatory cytokine in both acute and chronic inflammations which causes an inflammatory response through interaction with its receptors expressed on various cells like endothelial cells. (
  • Septic shock is induced by large-scale production of inflammatory cytokines, including TNF-alpha. (
  • Dysregulation of TNF-alpha expression is thought to be a critical pathogenic mechanism in numerous autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). (
  • The tumor necrosis factor alpha (TNF-a) inhibitors represent one of the major treatment methods for inflammatory diseases. (
  • The aim of this study was to investigate the potential therapeutic and toxic effect of the direct injection of the anti-TNF-α on oxidative stress mediators, proinflammatory cytokines and vascular risk factors associated with diabetes on diabetic rats. (
  • Tumor necrosis factor-alpha (TNF-alpha), which is expressed in the failing heart, may stimulate oxidative stress. (
  • In addition, TNF-alpha may stimulate oxidative stress in the failing heart in patients with DCM. (
  • Thus, oxidative stress may be an important susceptibility factor for dilated cardiomyopathy (DCM) (9,10) . (
  • Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. (
  • We find that 100 U/ml TNF-alpha/cachectin (TNF), a concentration attainable in the blood of humans with parasitic infestations, stimulates highly purified populations of EOs to damage human umbilical vein endothelial cells (HUVEC), a model of human endothelium. (
  • 1989 ). Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins. (
  • This sensitivity to TNFalpha was associated with a block in nuclear factor-kappaB-mediated cell survival signals. (
  • The aim of this study is to characterize the effect of tumor necrosis factor-alpha (TNFalpha) on epithelial barrier function in the colonic epithelial cell line HT-29/B6. (
  • OBJECTIVES: To investigate the effect of prolonged neutralisation of tumour necrosis factor alpha (TNFalpha) on the radiological course in rheumatoid arthritis (RA). (
  • Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1 beta and tumor necrosis factor alpha expression in cultured human astroglial cells by dexamethasone and indomethacin. (
  • The human tumor necrosis factor alpha (TNF-alpha) gene encodes a cytokine whose activities have been implicated in many immunopathological processes, including the activation and differentiation of lymphocytes. (
  • We report here that TNF-alpha gene transcription is rapidly and highly induced in three independently derived human Burkitt lymphoma cell lines, as well as in freshly isolated human splenic B cells, activated by antibodies to surface immunoglobulin. (
  • This burst in TNF-alpha gene transcription is associated with an induction of TNF-alpha bioactivity in the culture supernatants from stimulated splenic B cells. (
  • Moreover, induction of TNF-alpha gene transcription by anti-immunoglobulin was blocked by the immunosuppressants cyclosporin A and FK506. (
  • In order to enhance osseointegration of the implant in an inflamed environment, the small interfering RNA (siRNA) targeting tumor necrosis factor alpha (TNF-α) was used to functionalize titanium surface for gene silencing. (
  • This meta-analysis was performed to clarify the association between tumor necrosis factor alpha ( TNF-α ) gene polymorphisms and open angle glaucoma (OAG) risks, and the association between the TNF-α level in aqueous humor (AH) and the risks of glaucoma. (
  • Ohno I, Lea RG, Flanders KC, Clark DA, Banwatt D, Dolovich J, Denburg J, Harley CB, Gauldie J, Jordana M. Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1). (
  • In this study, we demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. (
  • We set out to determine which MAPK signaling pathways are activated in our system and which MAPK pathways are required for TNF-alpha gene transcription or TNF-alpha mRNA translation. (
  • This gene can be induced by proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-1. (
  • Tumour necrosis factor-alpha (TNFa) gene -308G/A polymorphism (rs1800629) are associated with psoriasis in several populations worldwide. (
  • Interestingly, when animals were treated with TNF-alpha inhibitors, or genetically engineered mice that could not produce TNF-alpha were studied, no damage occurred despite increased IOP. (
  • Although the complete pathophysiology of sarcoidosis is not well understood, it is known that tumor necrosis factor (TNF)-α plays a major role in sarcoidosis development, and TNF-α inhibitors have been used for the treatment of refractory sarcoidosis. (
  • Additionally, serum glucocorticoid bioactivity (GBA) or matrix metalloproteinases (MMP-7-9), their tissue inhibitors (TIMP-1-2), alpha-2-macroglobulin (α2M), human neutrophil elastase (HNE) and myeloperoxidase (MPO) were measured. (
  • This report studies the global Tumor Necrosis Factor Alpha Inhibitors market status and forecast, categorizes the global Tumor Necrosis Factor Alpha Inhibitors market size (value & volume) by manufacturers, type, application, and region. (
  • Focuses on the key Tumor Necrosis Factor Alpha Inhibitors manufacturers, to study the capacity, production, value, market share and development plans in future. (
  • In this study, the years considered to estimate the market size of Tumor Necrosis Factor Alpha Inhibitors are as follows: History Year: 2013-2017 Base Year: 2017 Estimated Year: 2018 Forecast Year 2018 to 2025 For the data information by region, company, type and application, 2017 is considered as the base year. (
  • Key Stakeholders Tumor Necrosis Factor Alpha Inhibitors Manufacturers Tumor Necrosis Factor Alpha Inhibitors Distributors/Traders/Wholesalers Tumor Necrosis Factor Alpha Inhibitors Subcomponent Manufacturers Industry Association Downstream Vendors Available Customizations With the given market data, QYResearch offers customizations according to the company's specific needs. (
  • The following customization options are available for the report: Regional and country-level analysis of the Tumor Necrosis Factor Alpha Inhibitors market, by end-use. (
  • In the present study, we investigated the effect of morphine on the release of tumor necrosis factor (TNF)-alpha from murine neonatal microglia. (
  • Del Pozo V, De Andres B, Martin E, Maruri N, Zubeldia JM, Palomino P, Lahoz C. Murine eosinophils and IL-1: alpha IL-1 mRNA detection by in situ hybridization. (
  • ORCID: and Allen, J 2008, 'The omega-3 fatty acid, eicosapentaenoic acid (EPA), prevents the damaging effects of tumour necrosis factor (TNF)-alpha during murine skeletal muscle cell differentiation' , Lipids in Health and Disease, 7 (1) , p. 24. (
  • Mice sensitized with D-galactosamine (GalN) and challenged with recombinant murine tumor necrosis factor α (TNFα) developed severe apoptotic and secondary necrotic liver injury as assessed by histology, measurement of cytosolic DNA fragments, and determination of liver specific enzymes in plasma. (
  • Elevation of cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in all of the patients studied. (
  • This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured. (
  • However, little is known about the probable relationship of serum TNF-alpha with major depressive disorder (MDD). (
  • To assess whether serum TNF-alpha levels could be associated with the clinical course of MDD. (
  • Detection of human serum tumor necrosis factor-alpha in healthy donors, using a highly sensitive immuno-PCR assay. (
  • A highly sensitive immunosensor based on ITO thin films covered by a new semi-conductive conjugated polymer for the determination of TNF alpha in human saliva and serum samples. (
  • OBJECTIVE: To measure serum concentration of six cytokines and growth factors suggested to have a role in tendon response to load among individuals with chronic Achilles tendinopathy and controls. (
  • Serum sickness-like reactions were seen in 2.5% of patients receiving TNF-alpha MAb. (
  • Serum tumour necrosis factor-alpha and soluble tumour necrosis factor receptors levels in patients with Guillain-Barre syndrome. (
  • [email protected] OBJECTIVES: To estimate the serum concentrations of Tumour Necrosis Factor alpha (TNF-alpha) and soluble TNF receptors (s TNF-RI and TNF-RII) in patients with Guillain-Barre syndrome (GBS), before and after treatment. (
  • Following the treatment (IVIG or PE), there was a significant decrease in the serum TNF-alpha concentrations (8.5-58.5 pg/ml) in these 41 GBS patients. (
  • CONCLUSIONS: The results of this indicated that (a) Elevated serum concentrations of TNF-alpha showed a positive correlation with the disease severity in patients with GBS. (
  • b) The decrease in the serum TNF-alpha and increase in the serum soluble TNF receptors, particularly sTNF-RII showed a positive correlation with the neurological recovery in GBB patients following treatment. (
  • These studies demonstrate that TNF-alpha production is an early event in B-cell activation and they establish the efficacy of using immunosuppressants as probes in dissecting transcriptional activation pathways in human B cells. (
  • Tumor necrosis factor (TNF)-alpha is postulated to play a major role in the pathogenesis of obesity-linked insulin resistance, probably resulting from an interaction with insulin signaling pathways. (
  • Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α) signaling pathways of the innate immune response are critical antimicrobial responses that have been highly conserved ( 37 ). (
  • Gut gavage with antiendotoxin antibodies reduces the liberation of tumor necrosis factor-alpha after hemorrhage/resuscitation. (
  • OBJECTIVE: To evaluate the effect of gut gavage both alone and with enteral administration of monoclonal antibodies to endotoxin on the liberation of tumor necrosis factor (TNF)-alpha and subsequent hemodynamics after hemorrhage/resuscitation. (
  • 05). CONCLUSIONS: Prior treatment with gut gavage and enterally administered antiendotoxin antibodies reduces TNF-alpha liberation after hemorrhage/resuscitation and confers a subsequent improvement in hemodynamics and decreased plasma lactate concentrations. (
  • 2) There are currently 5 monoclonal antibodies approved by the FDA for blockage of TNF-alpha as a clinical treatment. (
  • [13] Subsequently, in 1975 Lloyd J. Old from Memorial Sloan-Kettering Cancer Center , New York, reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF). (
  • We demonstrate that IFN-gamma production from SCID splenocytes is stimulated by interleukin (IL) 12, tumor necrosis factor alpha (TNF-alpha), and IL-2 but is inhibited by IL-10, IL-10, IL-12, and TNF are induced by heat-killed Listeria monocytogenes (hk-LM) from SCID splenocytes and peritoneal macrophages. (
  • Reactive oxygen species (ROS), DNA damage, superoxide dismutases (SOD) activity, tumor necrosis factor-alpha (TNF-α), and IL-6 were analyzed in CAP patients and LPS-stimulated macrophages cells. (
  • In our study we have determined that UK-14304 (UK) and norepinephrine (NE), both alpha 2-adrenergic agonists, can augment LPS-stimulated TNF from elicited macrophages (MO). (
  • This process is believed to be mediated by the upregulation of tumor necrosis factor alpha (TNF-α) production by macrophages. (
  • TNF-alpha production by LPS-stimulated macrophages is regulated at the levels of both transcription and translation. (
  • The aim of this study was to compare the TNF-alpha secretory profile of alveolar macrophages (AMs) and peripheral blood monocytes (Mos) of patients with cryptogenic FA and systemic sclerosis (SSc), a rheumatological disorder in which lung fibrosis can occur. (
  • In bacterial meningitis, LPS induces production in cerebrospinal fluid of the cytokines IL-1 beta and tumor necrosis factor alpha (TNF alpha), which are the principle mediators of meningeal inflammation. (
  • Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. (
  • Cohen T, Gitay-Goren H, Sharon R, Shibuya M, Halaban R, Levi BZ, Neufeld G (1995) VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells. (
  • 1987 ). Induction of receptors for tumor necrosis factor-by interferons is not a major mechanism for their synergistic cytotoxic response. (
  • The hypothesis is that a subset of patients with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME), including also patients with no clinical response after B-cell depletion therapy using the anti-CD20 antibody Rituximab, may benefit from tumor necrosis factor-alpha inhibition using Etanercept as weekly subcutaneous injections. (
  • Tumor Necrosis Factor-alpha Inhibition Using Etanercept in Moderate and Serious Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME), Including in Patients With no Clinical Response After B-lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab. (
  • An agonistic TNFR1 antibody completely mimicked the inhibitory action of TNF-alpha on insulin signaling, whereas at 100 pmol/l TNF-alpha, a nonagonistic p80 TNFR antibody, was shown to ameliorate the inhibitory action of the cytokine. (
  • 01) by anti-TNF-alpha antibody. (
  • This effect was also blocked by anti-TNF-alpha antibody. (
  • OBJECTIVE: This study, known as STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis), evaluated the safety and efficacy of adalimumab (Humira), a fully human monoclonal tumor necrosis factor-alpha (TNF-a) antibody, when given with standard antirheumatic therapy in patients with active rheumatoid arthritis (RA) not adequately responding to such therapies. (
  • Efficacy and Safety of Monoclonal Antibody to Human Tumor Necrosis Factor alpha in Patients With Sepsis Syndrome: A Randomized, Controlled, Double-blind, Multicenter Clinical Trial. (
  • Radiocurability by targeting tumor necrosis factor-alpha using a bispecific antibody in carcinoembryonic antigen transgenic mice. (
  • To overcome systemic side effects, we used a bispecific antibody (BsAb) directed against carcinoembryonic antigen (CEA) and TNF-alpha to target this cytokine in a CEA-expressing colon carcinoma. (
  • Our results showed statistically significant inhibition in DNA damage caused by BV treatment compared to corresponding TNF-alpha/Act D-treated hepatocytes. (
  • BV suppressed TNF-alpha/Act Dtreated activation of bcl-2 family and caspase family, which resulted in inhibition of cytochrome c release and PARP cleavage. (
  • The most extensive inhibition occurred in pretreated cells cultured at 37 degrees C. Cotreatment with LPS and dexamethasone also inhibited TNF alpha mRNA transcription at both temperatures. (
  • Preincubation of adipocytes with 5 nmol/l TNF-alpha for 15 min resulted in a 60-70% reduction of insulin action, reaching a stable inhibition (40%) after longer incubation with the cytokine. (
  • The modulation of insulin signaling by TNF-alpha was found to be paralleled by a comparable inhibition of insulin-stimulated glucose transport. (
  • These findings indicate that in human adipocytes, low concentrations of TNF-alpha induce a rapid inhibition of insulin signaling at the level of PI 3-kinase. (
  • Phenotypic differences among patients with the same CFTR genotype are most likely caused by differences in the function of such proteins and/or by environmental factors. (
  • The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-alpha) on intestinal epithelial cell permeability and the expression of tight junction proteins. (
  • Vascular endothelial growth factor antagonism restores epithelial barrier dysfunction via affecting zonula occludens proteins. (
  • c) This in vitro model does not demonstrate the rapid clearance of TNF-alpha from the circulation that is seen in vivo, suggesting that TNF-alpha metabolism does not occur primarily in the lung. (
  • The purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and particularly on the expression of IL-10, TNF-alpha and beta1 integrin. (
  • Earlier, we demonstrated that systemic blockade of nitric oxide (NO) generation by acute infusion of nitro-L-arginine methyl ester (L-NAME) in mice increases plasma and renal levels of tumor necrosis factor-alpha (TNF-α). (
  • Blockade of TNF-alpha function and downstream microglial activation may be an important approach for the treatment of glaucoma,' the investigators stated. (
  • Recombinant tumor necrosis factor-alpha potentiates neutrophil. (
  • Recombinant tumor necrosis factor-alpha potentiates neutrophil degranulation in response to host defense cytokines neutrophil-activating peptide 2 and IL-8 by modulating intracellular cyclic AMP levels. (
  • Apparently, other factors other than IOP may also play important roles in the pathogenesis of glaucomatous optic neuropathy. (
  • The effects of another antiinflammatory agent, indomethacin, on LPS induction of IL-1 beta and TNF alpha mRNA were temperature and cell line dependent. (
  • Furthermore, we demonstrate that dexamethasone, which inhibits the production of cytokines, including TNF-alpha, significantly inhibits LPS induction of JNK/SAPK activity but not that of p38, ERK1 and ERK2, or MEK3, MEK4, or MEK6. (
  • TNF-alpha also has some systemic effects, including induction of fever through action on the hypothalamus. (
  • Tumor necrosis factor plays an important role in the pathogenesis of AS disease that is accompanied by the loss of muscle strength. (
  • Finally, TNF-alpha augments LPS-induced IL-10 secretion. (
  • 1990 ). Tumor necrosis factor-alpha augments pulmonary arterial transendothelial albumin flux in vitro. (
  • Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells. (
  • Originally identified as a monocyte factor, our studies and those of others have demonstrated that B and T lymphocytes produce TNF-alpha when stimulated by a variety of inducers. (
  • Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis. (
  • Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. (
  • Accordingly, we cocultured purified human peripheral blood monocytes with a panel of cytokines including TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, granulocyte macrophage-CSF, transforming growth factor-beta, and IFN-alpha and then measured IL-10 mRNA production using a semiquantitative reverse transcription-polymerase chain reaction technique. (
  • In a previous study, we reported that salmonellae possess the ability to stimulate tumor necrosis factor alpha (TNF-α) accumulation in primary human monocytes, as well as in the human promonocytic cell line U38. (
  • Tumor necrosis factor (TNF)-alpha is expressed primarily by activated monocytes as part of the innate immune response to various microbes, gram-negative bacteria in particular. (
  • Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. (
  • The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. (
  • We have previously reported that gamma interferon and tumor necrosis factor alpha (TNF-α) synergistically inhibit HCMV replication in vitro. (
  • We investigated regulation of tenascin-C expression by TNF-alpha through nuclear factor-alphaB (NF-kappaB) in OA cartilage in vivo and in vitro. (
  • 1992 ). Interleukin-1 alpha and-beta augment pulmonary artery transendothelial albumin flux in vitro. (
  • PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) enhances radiotherapy (RT) killing of tumor cells in vitro and in vivo. (
  • In vitro, clonogenic assays were performed after RT alone, TNF-alpha alone, and RT plus TNF-alpha. (
  • RESULTS: In vitro, combined RT plus TNF-alpha resulted in a significant decrease in the survival fraction at 2 Gy compared with RT alone (p (
  • Following activation, MAPKs induce the expression of IL-1- and TNF-α-responsive genes by phosphorylating a number of transcription factors, including Jun, Fos, and ATF family members. (
  • Park JH et al: "Bee venom protects hepatocytes from tumor necrosis factor-alpha and actinomycin D." Archives of pharmacal research, vol. 33, no. 2, 2010, pp. 215-23, Accessed September 18, 2018. (
  • Bee venom protects hepatocytes from tumor necrosis factor-alpha and actinomycin D. Arch Pharm Res 2010;33(2):215-23 Accessed September 18, 2018. (
  • The "Tumor Necrosis Factor Alpha (TNF-a) Agonist - Pipeline Insight, 2018" drug pipelines has been added to's offering. (
  • Tumor Necrosis Factor Alpha (TNF-a) Agonist - Pipeline Insight, 2018 report offers comprehensive insights of the pipeline (under development) therapeutics scenario and growth prospects across Tumor Necrosis Factor Alpha (TNF-a) Agonist development. (
  • However, it has been clearly known that one of the important factors, activating pancreatic stellate cells during pancreatic injury, is proinflammatory cytokines known to be upregulated early in the course of acute pancreatic inflammation [ 3 , 4 ]. (
  • Tumor necrosis factor alpha (TNFα) possesses multipotent bioactivity that mediates various cellular responses, including proliferation, proinflammatory factor production, and cell death. (
  • Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been linked to breast cancer development. (
  • Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is upregulated in OA cartilage and is involved in the progression of OA, and stimulates tenascin-C expression in other types of cells. (
  • Also, exogenous IL-2 increases the response of NK cells to hk-LM or to IL-12 and TNF-alpha. (
  • It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. (
  • b) Increases in pulmonary arterial pressures seen in vivo with TNF-alpha administration are not due to a direct effect. (
  • NAP-2 and rIL-8 cooperated with TNF-alpha in very similar ways, as indicated by the almost identical increases in release rates that were induced by equipotent doses of either secondary stimulus. (
  • In this study we examined the expression pattern of TNF-alpha mRNA in adipose tissues from 18 control and 19 obese premenopausal women by Northern blot analysis. (
  • Furthermore, the effects of weight reduction by dietary treatment of obesity on the adipose expression of TNF-alpha mRNA were also analyzed in nine premenopausal obese women, before and after a controlled weight-reduction program. (
  • We found that TNF-alpha had a major effect on IL-10 mRNA production, inducing a 20- to 120-fold increase over baseline production. (
  • By in situ hybridization, 44-100% of the blood eosinophils from five patients with hypereosinophilia and four normal subjects exhibited intense hybridization signals for TNF-alpha mRNA. (
  • Most tissue eosinophils infiltrating nasal polyps were strongly positive for both TNF-alpha and MIP-1 alpha mRNA. (
  • By Northern blot analysis, highly enriched blood eosinophils from a patient with the idiopathic hypereosinophilic syndrome exhibited differential expression of TNF-alpha and MIP-1 alpha mRNA. (
  • Expression of mRNA and immunoreactivity for the granulocyte/macrophage colony-stimulating factor in activated human eosinophils. (
  • These data confirm that three MAPK family members and their upstream activators are stimulated by LPS and demonstrate that JNK/SAPK is required for LPS-induced translation of TNF-alpha mRNA. (
  • The stimulation of mRNA translation initiation rates, which occurs in response to decreased eIF-2α phosphorylation, may result in an increase in the translation of normally poorly translated mRNAs, such as those encoding growth factors or oncogenes. (
  • Measurements of endogenous TNF-alpha mRNA levels and evaluation of necrosis (histologic evaluation) were assessed per treatment group. (
  • The addition of exogenous TNF-alpha to RT significantly increased the endogenous TNF-alpha mRNA level, particularly when TNF-alpha was targeted with BsAb (p (
  • In order to further determine their potential biologic roles in inflammation, we studied their interaction with TNF-alpha-primed human polymorphonuclear neutrophil granulocytes at the levels of effector functions and signal transduction. (
  • These results demonstrate that low concentration BV possess a potent suppressive effect on anti-apoptotic responses of TNF-alpha/Act D-treated hepatocytes and suggest that these compounds may contribute substantial therapeutic potential for the treatment of liver diseases. (
  • 1978 ). Morphological factors influencing transepithelial permeability: a model for the resistance of the zonula occludens. (
  • The results emphasized that some immunological parameters, such as CRP, leukocyte count and TNF-alpha, are significantly involved in the clinical course and treatment response in MDD. (
  • this latter finding was corroborated by actinomycin-D time course studies, which showed that the half-life of IL-10 was less than 1 h and was not significantly altered by TNF-alpha. (
  • Plasma TNF-alpha levels were significantly higher in the CS than the AO with a significant positive correlation of the transcardiac gradient of TNF-alpha and the transcardiac gradient of oxLDL. (
  • More importantly, such calcium-mobilizing agents significantly enhanced TNF-alpha-induced IL-6 secretion while RANTES secretion was abrogated. (
  • Interestingly, TNF-alpha-induced interferon regulatory factor (IRF)-1 activation was significantly inhibited by all calcium-mobilizing agents, BK, Thr and Tg. (
  • The percentages of necrotic area were significantly augmented in the RT plus BsAb plus TNF-alpha group. (
  • The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). (
  • At baseline, osteoarthritic chondrocytes expressed significantly lower levels of beta1 integrin and higher levels and IL-10 and TNF-alpha levels. (
  • [24] [25] From this membrane-integrated form the soluble homotrimeric cytokine (sTNF) is released via proteolytic cleavage by the metalloprotease TNF alpha converting enzyme (TACE, also called ADAM17 ). (
  • Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of obesity through its overexpression in fat tissue. (
  • Finally, overexpression of wild-type SAPKbeta was able to overcome the dexamethasone-induced block of TNF-alpha translation. (
  • Eleven of the patients had at least one risk factor for LTBI (e.g., born in countries where TB is prevalent or contact with a person with TB disease). (
  • Three patients underwent a medical history for TB risk factors before beginning therapy with a TNF-α antagonist. (
  • The pulmonary phenotype in patients with cystic fibrosis (CF), even in those with the same CF transmembrane conductance regulator (CFTR) genotype, is variable and must therefore be influenced by secondary genetic factors as well as environmental factors. (
  • 6] To the best of our knowledge, the effects of anti-TNF-[alpha] treatment on muscle strength and endurance have not been studied in patients with AS yet. (
  • Therefore, in this study, we aimed to evaluate muscle performance by using isokinetic dynamometer before and at third month of anti-TNF-[alpha] treatment in ankylosing spondylitis patients. (
  • Tumor Necrosis Factor-producing T-regulatory Cells Are Associated With Severe Liver Injury in Patients With Acute Hepatitis A. Gastroenterology. (
  • Dr. Miller speculated that approaching glaucoma through the TNF-alpha pathway is likely to require chronic treatment in patients. (
  • Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1. (
  • Aim of the study was to evaluate tumour necrosis factor α (TNF-α) axis and oxidative status in patients with anorexia nervosa (AN) seeking a possible correlation with both nutritional status and evolution of the disease. (
  • Levels of tumor necrosis factor-alpha and interleukin-6 in severely ill patients with eating disorders. (
  • Intervention Patients were prospectively stratified into shock or nonshock groups and then randomized to receive a single infusion of 15 mg/kg of TNF-alpha MAb, 7.5 mg/kg of TNF-alpha MAb, or placebo. (
  • Results The distribution of variables describing demographics, organ system dysfunction or failure, preinfusion Acute Physiology and Chronic Health Evaluation II score, number of organs failing at baseline, initial sites of infection, infecting microorganisms, antimicrobials used, and initial invasive procedures was similar among patients in the TNF-alpha MAb and placebo treatment arms. (
  • Among all infused patients, there was no difference in all-cause mortality in patients who received placebo as compared with those who received TNF-alpha MAb. (
  • Conclusions There was no decrease in mortality between placebo and TNF-alpha MAb in all infused patients. (
  • In septic shock patients who received TNF-alpha MAb, a significant reduction in mortality was present 3 days after infusion. (
  • Although a trend toward reduced mortality continued at 28 days following treatment with TNF-alpha MAb, the difference in mortality among shock patients treated with placebo or TNF-alpha MAb was not significant. (
  • In particular, we wished to assess whether TNF-alpha levels differ between SSc patients with FA (FASSc) and a nonfibrotic group. (
  • Conversely, tumour necrosis factor-α antagonism did not affect cyclooxygenase-2 expression. (
  • Thus, these data indicate that macrophage production of TNF-alpha and IL-12 stimulates the release of IFN-gamma by NK cells and that IL-10 produced in response to hk-LM inhibits this response at the level of the macrophage and the NK cell. (
  • These findings suggest that morphine primes microglia for enhanced production of TNF-alpha which could alter several functional activities of these cells within the brain. (
  • A variety of dried plant seeds raise adiponectin levels and decrease tumor necrosis factor. (
  • Following ESW application, while beta1 integrin expression remain unchanged, a significant decrease of IL-10 and TNF-alpha intracellular levels was observed both in osteoarthritic and healthy chondrocytes. (
  • This treatment resulted in increased levels of TNF-alpha that, in turn, caused microglial activation, loss of the oligodendrocytes in the optic nerve, and delayed loss of retinal ganglion cells. (
  • When treated with double-stranded RNA (dsRNA), ΔTPR6-expressing cells exhibited a significant increase in eukaryotic initiation factor 2α phosphorylation and NF-κB activation, indicating a functional PKR. (
  • CONCLUSION: TNF-alpha stimulated tenascin-C expression through NF-kappaB signaling with RelA activation in cultured OA chondrocytes, suggesting involvement of tenascin-C in OA cartilage remodeling. (
  • The primary function of TNF-alpha is to recruit other leukocytes to the site of infection and to stimulate their activation. (
  • Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. (
  • Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that all stimulate the acute phase reaction. (
  • Tumour necrosis factor α (TNFα), an endogenous factor of the lung involved in host defence, 6 is therefore a possible modulator of CF pulmonary disease severity. (
  • In contrast, IL-10 inhibits hk-LM-induced IFN-gamma production at two levels: (i) by inhibiting TNF and IL-12 production from these cultures (presumably from the macrophage) and (ii) by inhibiting the stimulatory effects of IL-12 and TNF-alpha on NK-cell IFN-gamma production. (
  • The aim of this study was to assess whether tumor necrosis factor alpha (TNF-α) levels are correlated with the behavioral syndrome of schizophrenia and/or metabolic abnormalities. (
  • No significant correlation was found between CSF TNF-α levels and the Positive and Negative Syndrome Scale total scores or other factors scores. (
  • TNF-alpha levels were constant throughout the 2-hr period in the experimental group, and no TNF-alpha was detected in the perfusion medium of the control group. (
  • In a control group of mice with normal IOP levels, the same sequence of events was observed after injection of TNF-alpha. (
  • 1 , 2 SCA is characterized by a variable clinical course and differences in response to medication, reflecting its complex pathophysiology and suggesting that it can be affected by modulator factors such as the haplotypes of the beta globin chain or fetal hemoglobin (Hb F) levels. (
  • We also measured the plasma levels of TNF-alpha and angiotensin II. (
  • Direct measurement of intracellular cAMP revealed that TNF-alpha by itself did not affect its levels. (
  • After that, chondrocytes were cultured in 24-well plate in DMEM supplemented with 10% FCS for 48 hours and then beta 1 integrin surface expression and intracellular IL-10 and TNF-alpha levels were evaluated by flow-cytometry. (
  • IL-10 levels decreased at any impulses and energy levels, while a significant reduction of TNF-alpha was mainly found at middle energies. (
  • Our study confirmed that osteoarthritic chondrocytes express low beta 1 integrin and high TNF-alpha and IL-10 levels. (
  • Nonetheless, ESW treatment application down-regulate the intracellular levels of TNF-alpha and IL-10 by chondrocytes, suggesting that ESW might restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels. (
  • 1, 2 Certain phenotypes of CF are clearly associated with different CF transmembrane conductance regulator (CFTR) genotypes such as pancreatic insufficiency, but pulmonary disease is strongly influenced by other factors. (