Tumor Necrosis Factor-alpha: 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.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Receptors, Tumor Necrosis Factor, Type I: 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.Receptors, Tumor Necrosis Factor, Type II: 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.Interleukin-1: 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.Cytokines: 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.Lipopolysaccharides: 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)Interleukin-6: 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, Cultured: 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.Necrosis: 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.NF-kappa B: 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, Messenger: 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.Interferon-gamma: 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.Macrophages: 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.)Lymphotoxin-alpha: 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.Mice, Inbred C57BLCell Line: Established cell cultures that have the potential to propagate indefinitely.Monocytes: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Signal Transduction: 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.Apoptosis: 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.Inflammation: 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.Mice, Inbred BALB CGene Expression Regulation: 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.Tumor Necrosis Factors: 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, Monoclonal: Antibodies produced by a single clone of cells.Arthritis, Rheumatoid: 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.Transforming Growth Factor alpha: 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.Interleukin-10: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Interleukin-8: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Tumor Necrosis Factor Decoy Receptors: 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.Molecular Sequence Data: 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.Antirheumatic Agents: Drugs that are used to treat RHEUMATOID ARTHRITIS.Mice, Knockout: 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.Antigens, CD: 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.Macrophage Activation: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Synovial Membrane: 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.Disease Models, Animal: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Line, Tumor: A cell line derived from cultured tumor cells.Up-Regulation: 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.Leukocytes, Mononuclear: 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.Interleukin-1beta: 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.Enzyme-Linked Immunosorbent Assay: 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.Tumor Cells, Cultured: 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.Transfection: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Neutrophils: 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.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Endotoxins: 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.Macrophages, Peritoneal: Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum.Flow Cytometry: 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.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Cell Survival: 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.I-kappa B Proteins: 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.T-Lymphocytes: 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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Blotting, Western: 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.Down-Regulation: 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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Pentoxifylline: 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.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Promoter Regions, Genetic: 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.Enzyme Activation: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.I-kappa B Kinase: 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.TNF Receptor-Associated Factor 2: 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.Mice, Inbred C3HInterleukin-12: 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.Nitric Oxide: 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.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Transcription Factor RelA: 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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Intercellular Adhesion Molecule-1: 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.Granulocyte-Macrophage Colony-Stimulating Factor: 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.Tumor Markers, Biological: 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.Receptors, Cell Surface: 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.Kinetics: The rate dynamics in chemical or physical systems.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Tumor Necrosis Factor Receptor-Associated Peptides and Proteins: Intracellular signaling peptides and proteins that bind directly or indirectly to the cytoplasmic portion of TUMOR NECROSIS FACTOR RECEPTORS.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Antigens, CD14: 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.TNF-Related Apoptosis-Inducing Ligand: 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.Interleukins: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Shock, Septic: 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.Polymerase Chain Reaction: 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.Antibodies: 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).p38 Mitogen-Activated Protein Kinases: 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.Lymphocyte Activation: 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.Dendritic Cells: 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).Mitogen-Activated Protein Kinases: 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).Caspases: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Tumor Burden: The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.TNF Receptor-Associated Factor 1: 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.Biological Markers: 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.DNA Primers: 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.Nitric Oxide Synthase Type II: 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.Protein Binding: 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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Interleukin 1 Receptor Antagonist Protein: 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.Interleukin-1alpha: 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.Blotting, Northern: 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.Proteins: 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.Rats, Sprague-Dawley: 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.ADAM Proteins: 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, Experimental: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.DNA-Binding Proteins: 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.JNK Mitogen-Activated Protein Kinases: 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.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Dinoprostone: 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.Antigens, CD95: 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.GalactosamineCell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Macrophages, Alveolar: 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.Toll-Like Receptor 4: A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.Amino Acid Sequence: 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.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Membrane Proteins: 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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Fibrosarcoma: 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)Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Cell Adhesion Molecules: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Apoptosis Regulatory Proteins: 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.Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system.Caspase 8: 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.Epithelial Cells: 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 Fusion Proteins: 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.Chemokines: 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.Mutation: 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.Toll-Like Receptor 2: 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.Interleukin-4: 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.Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Toll-Like Receptors: 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.HeLa Cells: 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.Cell Adhesion: Adherence of cells to surfaces or to other cells.Chemokine CCL2: 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.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Anti-Inflammatory Agents, Non-Steroidal: 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.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Coculture Techniques: 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.TNF Receptor-Associated Factor 6: 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.Synovial Fluid: The clear, viscous fluid secreted by the SYNOVIAL MEMBRANE. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints.Mice, Inbred DBALeukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Vascular Cell Adhesion Molecule-1: 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)Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.E-Selectin: 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.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Receptors, Interleukin-1: 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.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Treatment Outcome: 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.CD4-Positive T-Lymphocytes: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.DNA: 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).U937 Cells: 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.Transforming Growth Factor beta: 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.RNA, Small Interfering: 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.Mice, Inbred Strains: 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.Cell Nucleus: 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)Tumor Suppressor Protein p53: 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.Arthritis, Psoriatic: 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.Caspase 3: 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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Receptor-Interacting Protein Serine-Threonine Kinases: 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.Cytotoxicity, Immunologic: 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.Polymyxin B: 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, SCID: 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.Cattle: 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.Immunity, Innate: 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.Receptors, Tumor Necrosis Factor, Member 25: 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.Umbilical Veins: 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.Neoplasm Proteins: 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.Sphingomyelin Phosphodiesterase: 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 3.1.4.12.Tristetraprolin: 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.Chemotherapy, Cancer, Regional Perfusion: 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, Conditioned: 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).Sarcoma, Experimental: Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA.Fas Ligand Protein: 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.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Ceramides: 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.Endothelial Cells: 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.Spondylitis, Ankylosing: 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: 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.Kupffer Cells: 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.Nitrites: 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)Wilms Tumor: 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.

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. ...
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 - 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.
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
Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock protein 72 in human peripheral blood mononuclear cells.
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.
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 ...
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 ...
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. ...
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. ...
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 ...
TY - JOUR. T1 - Dermatologists awareness of and screening practices for hepatitis B virus infection before initiating tumor necrosis factor-α inhibitor therapy. AU - Stine, Jonathan. AU - Bass, Michael. AU - Ibrahim, Dalia. AU - Khokhar, Omar S.. AU - Lewis, James H.. PY - 2011/12/1. Y1 - 2011/12/1. N2 - OBJECTIVE: The aim of the study was to assess dermatologists awareness of available guidelines and drug package insert information on the screening for and management of hepatitis B (HBV) infection in patients receiving tumor necrosis factor-α inhibitor (TNF-αI) drug therapies for dermatological disorders. MATERIALS AND METHODS: An electronic descriptive cross-sectional questionnaire was administered to a random, nationwide sample of physician members of the American Academy of Dermatology. Each participating physician answered 8 questions regarding his or her awareness of the risk of HBV reactivation. RESULTS: More than half of the dermatologists surveyed (52%) were aware of guidelines ...
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 ...
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, ...
TY - JOUR. T1 - Tumor necrosis factor-α-induced caspase activation mediates endotoxin-related cardiac dysfunction. AU - Carlson, Deborah L.. AU - Willis, Monte. AU - White, D. Jean. AU - Norton, Jureta W.. AU - Giroir, Brett P.. PY - 2005/5/1. Y1 - 2005/5/1. N2 - Objective: Sepsis-induced cardiac dysfunction is a serious clinical syndrome characterized by hypotension, decreased systemic vascular resistance, and elevated cardiac index. Although cytokines such as tumor necrosis factor (TNF)-α have been shown to play a significant role early in this response, the downstream effects of TNF-α signaling on cardiac function, specifically its relationship to apoptosis, have not been fully elucidated. Design: Previous studies from our laboratory have identified endotoxin-induced apoptosis in cardiac cells in vitro. To further determine the role of lipopolysaccharide-induced apoptosis in vivo, mice were injected intraperitoneally with lipopolysaccharide (4 mg/kg), and cardiac apoptosis was detected and ...
Clinical trial for Rheumatoid Arthritis , Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis
The IUPHAR/BPS Guide to Pharmacology. OX40 - Tumour necrosis factor (TNF) receptor family. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Blocking the proinflammatory cytokine tumor necrosis factor-alpha failed to stop overall structural progression of hand osteoarthritis, a randomized trial found.
If patients could recognise themselves, or anyone else could recognise a patient from your description, please obtain the patients written consent to publication and send them to the editorial office before submitting your response [Patient consent forms] ...
Introduction In 2008, the Food and Drugs Administration required manufacturers of TNFα antagonists to strengthen their warnings about the risk of serious fungal infections in patients with rheumatoid...
Title:Insulin-Sensiting Effects of Tumor Necrosis Factor Alpha Inhibitors in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. VOLUME: 13 ISSUE: 3. Author(s):Christian Leporini*, Emilio Russo, Salvatore D`Angelo, Franco Arturi, Giovanni Tripepi, Rosario Peluso, Rosa Daniela Grembiale, Ignazio Olivieri, Giovambattista De Sarro and Francesco Ursini. Affiliation:Department of Health Sciences, University of Catanzaro , Department of Health Sciences, University of Catanzaro , Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, Department of Health Sciences, University of Catanzaro , CNRIBIM, National Research Council-Institute of Biomedicine, Reggio Calabria, Department of Clinical Medicine and Surgery - Rheumatology Research Unit - Federico II University, Naples, Department of Health Sciences, University of Catanzaro , Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of ...
T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-α (TNF-α). Protein kinase C-θ (PKC-θ) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-θ was sequestered away from the Treg immunological synapse. Furthermore, PKC-θ blockade enhanced Treg function, demonstrating PKC-θ inhibits Treg-mediated suppression. Inhibition of PKC-θ protected Treg from inactivation by TNF-α, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-θ-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.. ...
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Data on interleukin-6 (IL-6) and tumour necrosis factor-a (TNF-a) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL-6 and TNF-a release during exercise. We have now studied the temporal relationship of leg IL-6 and TNF-a release before and during isolated two-legged exercise after 14 days of one-leg immobilization (IM) while the other leg served as the control (CON) leg. Fifteen healthy male subjects (mean ± SEM age, 23 ± 1 years; body mass index, 23.6 ± 0.7 kg m; and maximal oxygen uptake, 46.8 ± 1.4 ml kg min) performed 45 min of two-legged dynamic knee-extensor exercise at 19.6 ± 0.8 W. Arterial and femoral venous blood samples from the CON and the IM leg were collected every 15 min during exercise, and leg blood flow was measured with Doppler ultrasound. The arterial plasma IL-6 concentration increased (P ,0.05) with exercise (rest, 1.3 ± 0.1 pg ...
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Exposure of the airways to air toxins initiates transient and reversible airway injury to both adults and young children. Repetitive exposures of children residing within high oxidant communities leads to impairment of lung growth and pulmonary function, and remodeling of airway epithelial tissues is also suggested to occur. In the completely normal/healthy airway, exposure to ozone (O3), a ubiquitous urban air pollutant, induces an inflammatory response that is characterized by increases in epithelial permeability, neutrophilic infiltration, and bronchial hyperreactivity. Inhalation by humans of the pleiotropic pro-inflammatory cytokine tumor necrosis factor (Tnf) leads to the development of nearly identical responses: hyperresponsiveness of the bronchial airway (AHR), and neutrophil influx. Using controlled exposure to O3 in a laboratory setting, we have recently established a link between a genetic single nucleotide polymorphism (SNP) of TNF gene (-308) and the development of AHR to ...
Exposure of the airways to air toxins initiates transient and reversible airway injury to both adults and young children. Repetitive exposures of children residing within high oxidant communities leads to impairment of lung growth and pulmonary function, and remodeling of airway epithelial tissues is also suggested to occur. In the completely normal/healthy airway, exposure to ozone (O3), a ubiquitous urban air pollutant, induces an inflammatory response that is characterized by increases in epithelial permeability, neutrophilic infiltration, and bronchial hyperreactivity. Inhalation by humans of the pleiotropic pro-inflammatory cytokine tumor necrosis factor (Tnf) leads to the development of nearly identical responses: hyperresponsiveness of the bronchial airway (AHR), and neutrophil influx. Using controlled exposure to O3 in a laboratory setting, we have recently established a link between a genetic single nucleotide polymorphism (SNP) of TNF gene (-308) and the development of AHR to ...
The present invention relates to ligands which bind to human tumor necrosis factor alpha (TNF) in a manner such that upon binding of these ligands to TNF the biological activity of TNF is modified. In preferred forms the ligand binds to TNF in a manner such that the induction of endothelial procoagulant activity of the TNF is inhibited; the binding of TNF to receptors on endothelial cells is inhibited; the induction of fibrin deposition in the tumor and tumor regression activities of the TNF are enhanced; and the cytotoxicity and receptor binding activities of the TNF are unaffected or enhanced on tumor cells. The ligand is preferably an antibody, F(ab) fragment, single domain antibody (dABs) single chain antibody or a serum binding protein. It is preferred, however, that the ligand is a monoclonal antibody or F(ab) fragment thereof.
The team reported that 96 had indeterminate colitis from the Cambridge/Eastern panel in the United Kingdom.. The research team also included 760 healthy control subjects.. The team assessed DLG5_113G/A, DLG5_4136C/A, tumor necrosis factor-857C/T, and tumor necrosis factor-1031T/C polymorphisms.. Known Crohns disease-predisposing variants in CARD15/NOD2 were also genotyped to permit analysis for reported epistatic interactions.. Tumor necrosis factor-857 was shown to be associated with IBD overall.. A formal interaction test showed that tumor necrosis factor-857 is associated equally with ulcerative colitis and Crohns disease.. The research team found that neither of the DLG5 alleles, however, was associated with IBD.. Subgroup analysis also failed to show evidence of association between either DLG5 allele or genotype frequencies and ulcerative colitis or Crohns disease.. Stratification of tumor necrosis factor-alpha and DLG5 cases by CARD15 genotype made no significant difference in the ...
TY - JOUR. T1 - Tumor-nekrose-faktor alpha bei chronischer herzinsuffizienz. Klinische manifestation und therapeutische möglichkeiten. AU - Genth-Zotz, Sabine. AU - Bolger, Aidan P.. AU - Anker, Stefan D.. PY - 2001. Y1 - 2001. N2 - Background: Chronic heart failure (CHF) may be seen as a multi-system disorder with its origin in the heart but including many extracardiac manifestations. Immunological abnormalities are recognized in this context, in particular, changes in the expression of mediators of the innate immune response. Importance of TNF: Higher levels of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF) are found in the circulation and in the myocardium of patients with chronic heart failure than in controls. TNF has been implicated in a number of pathophysiological processes that are thought to be important to the progression of chronic heart failure. Therapies directed against this cytokine might therefore represent anovel approach to heart failure management.. AB - ...
Effects of Tumor Necrosis Factor-a on Insulin Stimulated Amino Acid Transport in Cultured Rat Hepatocytes. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
While monoclonal antibodies against tumor necrosis factor-α (TNFα) are effective in treating Crohns disease (CD), approximately one-third
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 ...
... 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 ...
Chen P, Mayne M, Power C, Nath A (September 1997). "The Tat protein of HIV-1 induces tumor necrosis factor-alpha production. ... Mayne M, Bratanich AC, Chen P, Rana F, Nath A, Power C (1998). "HIV-1 tat molecular diversity and induction of TNF-alpha: ... AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an ...
... called tumor necrosis factor alpha (TNF), is released not only by the herniated disc, but also in cases of disc tear (annular ... "Tumor necrosis factor-alpha modulates matrix production and catabolism in nucleus pulposus tissue". Spine. 30 (17): 1940-8. doi ... Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral ... It can show the spinal cord, nerve roots, and surrounding areas, as well as enlargement, degeneration, and tumors. It shows ...
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 ...
... 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" ...
"Extracts of mosquito salivary gland inhibit tumour necrosis factor alpha release from mast cells". Parasite Immunology. 15 (1 ... Alpha-glucosidase activity is elevated in the posterior midgut after feeding in response to the blood meal, whereas activity in ... Alpha-glucosidase is active in anterior and posterior midguts before and at all times after feeding. In whole midgut ... Early work described a factor in saliva that directly suppresses TNF-α release, but not antigen-induced histamine secretion, ...
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 ...
"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 ...
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] ...
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 ...
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 ...
Cellular basis for the negative inotropic effect of tumor necrosis factor alpha in the adult mammalian heart. J Clin Invest ... micropinocytosis infecting perivascular macrophages which produce additional virus and cytokines such as tumour necrosis factor ... Interferon-alpha can cause arrhythmia and myocardial infarction/ischemia. Mortality in HIV-infected patients with ... Alternatively, the immunoglobulins can reduce the effects or secretions of cytokines and cellular growth factors. Signs and ...
"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 ...
de 2000). «Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II». J. ... Isolation and characterization of human cDNA clones encoding the alpha and the alpha' subunits of casein kinase II». ... Entrez Gene: CSNK2A1 casein kinase 2, alpha 1 polypeptide». *↑ Kristensen, Lars P; Larsen Martin R, Højrup Peter, Issinger Olaf ... de 1998). «Casein kinase II interacts with the bZIP domains of several transcription factors». Nucleic Acids Res. (ENGLAND) 26 ...
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 ...
Altschuler EL, Kast RE (2003). „Bupropion in psoriasis and atopic dermatitis: decreased tumor necrosis factor-alpha?". ...
"Tumor necrosis factor-alpha inhibitor treatment for sarcoidosis". Therapeutics and Clinical Risk Management. 4 (6): 1305-13. ... Cathcart S, Sami N, Elewski B; Sami; Elewski (May 2012). "Sarcoidosis as an adverse effect of tumor necrosis factor inhibitors ... 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. Athens, Greece. 28 (6 ...
"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 ...
... and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome". J. Nutr. Biochem. 15 (6): 350-57. doi:10.1016 ...
... transactivates the epidermal growth factor receptor through specific E-prostanoid receptors and tumor necrosis factor-alpha ... a critical growth factor involved in normal mammary gland development. In addition, agonists of the epidermal growth factor ... Kleinberg DL, Wood TL, Furth PA, Lee AV (2009). "Growth hormone and insulin-like growth factor-I in the transition from normal ... Ibrahim YH, Yee D (2004). "Insulin-like growth factor-I and cancer risk". Growth Horm. IGF Res. 14 (4): 261-9. doi:10.1016/j. ...
"Stimulation of IRF-7 gene expression by tumor necrosis factor alpha: requirement for NFkappa B transcription factor and gene ... Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription ... IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription factor (IRF) family. IRF7 has ... Interferon regulatory factors. References[edit]. *^ a b c ENSG00000185507 GRCh38: Ensembl release 89: ENSG00000276561, ...
... such as tumor necrosis factor alpha (TNF-α), direct protein loss, particularly myosin heavy chain protein, in C2C12 skeletal ... myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha". ... to growth factors. The scaffolding of C2C12 cells is particularly important for studying muscle tissue regeneration post-injury ...
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 ...
The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral ... The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral ... The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral ... The Flavonoid Quercetin Inhibits Proinflammatory Cytokine (Tumor Necrosis Factor Alpha) Gene Expression in Normal Peripheral ...
Tumor Necrosis Factor Receptor 1 or Tumor Necrosis Factor Receptor Type I or p55 or p60 or CD120a - Market research report and ... Tumor necrosis factor receptor 1 (TNFR1) is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFalpha). ... Tumor Necrosis Factor Receptor Superfamily Member 1A (Tumor Necrosis Factor Receptor 1 or Tumor Necrosis Factor Receptor Type I ... Tumor Necrosis Factor Receptor Superfamily Member 1A (Tumor Necrosis Factor Receptor 1 or Tumor Necrosis Factor Receptor Type I ...
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) ...
Tuberculosis associated with infliximab, a tumor necrosis factor-alpha neutralizing agent. N Engl J Med 2001;345:1098--104. ... Tuberculosis Associated with Blocking Agents Against Tumor Necrosis Factor-Alpha --- California, 2002--2003. ... disease is a potential adverse reaction from treatment with the tumor necrosis factor-alpha (TNF-α) antagonists infliximab ( ... Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003; ...
Rapid acceleration of neutrophil apoptosis by tumor necrosis factor-alpha.. Takeda Y1, Watanabe H, Yonehara S, Yamashita T, ... We demonstrate here that human necrosis factor-alpha, a potent neutrophil activator, induces rapid (within 3 h) apoptosis of ...
Mus musculus tumor necrosis factor, alpha-induced protein 3 (Tnfaip3), transcrip... Mus musculus tumor necrosis factor, alpha- ... Mus musculus tumor necrosis factor, alpha-induced protein 3 (Tnfaip3), transcript variant 2, mRNA. NCBI Reference Sequence: NM_ ... See the reference protein sequence for tumor necrosis factor alpha-induced protein 3 isoform 2 (NP_001159874.1). ... Ovarian tumor domain proteases Ovarian tumor domain proteasescomputationally inferred pathway (not manually curated) ... [ ...
Proteins matched: Tumour necrosis factor alpha (IPR002959) The following proteins are predicted to be part of this family: ... Tumor necrosis factor. Macropus eugenii (Tammar wallaby). Loading... P01375 3D Tumor necrosis factor. Homo sapiens (Human). ... Tumor necrosis factor. Oryctolagus cuniculus (Rabbit). Loading... P06804 3D Tumor necrosis factor. Mus musculus (Mouse). ... Tumor necrosis factor. Papio sp. (Baboon). Loading... P36939 Tumor necrosis factor. Peromyscus leucopus (White-footed mouse). ...
12 Abstracts with Tumor Necrosis Factor (TNF) Alpha Enhancer Research. Filter by Study Type. Animal Study. ... Pharmacological Actions : Antiviral Agents, Tumor Necrosis Factor (TNF) Alpha Enhancer. Additional Keywords : Cytokine ... Pharmacological Actions : Antiviral Agents, Tumor Necrosis Factor (TNF) Alpha Enhancer. Additional Keywords : Cytokine ... Pharmacological Actions : Immunomodulatory, Immunostimulatory, Tumor Necrosis Factor (TNF) Alpha Enhancer. Additional Keywords ...
Tumor necrosis factor alphaImported. ,p>Information which has been imported from another database using automatic procedures.,/ ... tr,B5BUQ6,B5BUQ6_HUMAN Tumor necrosis factor alpha (Fragment) OS=Homo sapiens GN=TNF PE=2 SV=1 ... IPR002959. TNF_alpha. IPR021184. TNF_CS. IPR006052. TNF_dom. IPR008983. Tumour_necrosis_fac-like_dom. ... IPR002959. TNF_alpha. IPR021184. TNF_CS. IPR006052. TNF_dom. IPR008983. Tumour_necrosis_fac-like_dom. ...
Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα, cachexin, or cachectin) is a cell signaling protein (cytokine) ... Tumor Necrosis Factor-alpha at the US National Library of Medicine Medical Subject Headings (MeSH) Biology portal Medicine ... reported another cytotoxic factor produced by macrophages and named it tumor necrosis factor (TNF). Both factors were described ... Tumor necrosis factor (TNF) alpha increases collagen accuulation and proliferation in intestinal myofibrobasts via TNF Receptor ...
... tumor necrosis factor alpha include Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold ... Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune ... Tumor Necrosis Factor-alpha: 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 ...
PubMed journal article Bee venom protects hepatocytes from tumor necrosis factor-alpha and actinomycin were found in PRIME ... Tumor Necrosis Factor-alpha. Pub Type(s). Journal Article. Research Support, Non-U.S. Govt. Language. eng ... TY - JOUR T1 - Bee venom protects hepatocytes from tumor necrosis factor-alpha and actinomycin D. AU - Park,Ji-Hyun, AU - Kim, ... Nitric oxide prevents tumor necrosis factor alpha-induced rat hepatocyte apoptosis by the interruption of mitochondrial ...
... Back to search result Supplier. Cedarlane. Productcode. CLCYT008-2. Product ...
Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.. G S Hotamisligil, ... Similar increases were also observed in adipose production of TNF-alpha protein but circulating TNF-alpha levels were extremely ... TNF-alpha protein concentrations in plasma and in conditioned medium of explanted adipose tissue were measured by ELISA. ... Recent studies in animal models have indicated that TNF-alpha plays an important role in mediating the insulin resistance of ...
Tumor Necrosis Factor-alpha Inhibition Using Etanercept in Chronic Fatigue Syndrome. This study has been terminated. ... Tumor Necrosis Factor-alpha Inhibition Using Etanercept in Moderate and Serious Chronic Fatigue Syndrome/ Myalgic ... may benefit from tumor necrosis factor-alpha inhibition using Etanercept as weekly subcutaneous injections. ... Necrosis. Fatigue Syndrome, Chronic. Encephalomyelitis. Myalgia. Disease. Pathologic Processes. Signs and Symptoms. Virus ...
Polymorphisms in Tumour Necrosis Factor Alpha (TNF. ) Gene in Patients with Acute Pancreatitis. Gül Özhan,1 Hakan T. Yanar,2 ... T. Spies, C. Morton, and S. A. Nedospasov, "Genes for tumour necrosis factor alpha and beta are linked to the major ... H. Beranek, N. Teich, H. Witt et al., "Analysis of tumour necrosis factor alpha and interleukin 10 promotor variants in ... Tumour necrosis factor (TNFα), thought to be the first cytokine released, is a principal mediator of immune responses [6]. The ...
... leukocyte count and TNF-alpha, are significantly involved in the clinical course and treatment response in MDD. TNF-alpha in ... interleukin-6 and tumor necrosis factor-alpha (TNF-alpha). However, little is known about the probable relationship of serum ... Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder Psychopharmacology (Berl ... TNF-alpha with major depressive disorder (MDD). Objective: To assess whether serum TNF-alpha levels could be associated with ...
Abstract 707: Tumor Necrosis Factor-alpha p75 Receptor, Sattelite-Cell Activation and Neovascularization. David A Goukassian, ... Abstract 707: Tumor Necrosis Factor-alpha p75 Receptor, Sattelite-Cell Activation and Neovascularization ... Abstract 707: Tumor Necrosis Factor-alpha p75 Receptor, Sattelite-Cell Activation and Neovascularization ... Abstract 707: Tumor Necrosis Factor-alpha p75 Receptor, Sattelite-Cell Activation and Neovascularization ...
Furthermore, we have demonstrated that the tumor necrosis factor-α modulation of KNa channels does not occur at the level of ... Here, using cultured DH neurons, we have shown that tumor necrosis factor-α inhibits the total outward potassium current IK ... Tumor necrosis factor alpha modulates sodium-activated potassium channel SLICK in rat dorsal horn neurons via p38 MAPK ... Tumor necrosis factor α modulates sodium-activated potassium channel SLICK in rat dorsal horn neurons via p38 MAPK activation ...
Characterization of a novel tumor necrosis factor-alpha-induced endothelial primary response gene.. [F W Wolf, R M Marks, V ... The response of endothelial cells to the cytokine tumor necrosis factor-alpha (TNF) is complex, involving the induction and ...
... 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 ... Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in ... Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in ... Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in ...
The human tumor necrosis factor alpha (TNF-alpha) gene encodes a cytokine whose activities have been implicated in many ... Transcription of the tumor necrosis factor alpha gene is rapidly induced by anti-immunoglobulin and blocked by cyclosporin A ... Transcription of the tumor necrosis factor alpha gene is rapidly induced by anti-immunoglobulin and blocked by cyclosporin A ... Transcription of the tumor necrosis factor alpha gene is rapidly induced by anti-immunoglobulin and blocked by cyclosporin A ...
Tumor necrosis factor alpha (TNF-α) is a cytokine with significance in early diagnosis of cardiovascular diseases, obesity and ... Tumor necrosis factor alpha (TNF-α) is a cytokine with significance in early diagnosis of cardiovascular diseases, obesity and ... Rapid and sensitive SERS detection of the cytokine tumor necrosis factor alpha (tnf-α) in a magnetic bead pull-down assay with ... Detection of human serum tumor necrosis factor-alpha in healthy donors, using a highly sensitive immuno-PCR assay. Clin Chem. ...
... cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha ... Tumor necrosis factor α (TNF), initiates a cytokine cascade that promotes hepatocyte proliferation after 70% partial ... Hidetake Amemiya, Hiroshi Kono, Hideki Fujii, Liver Regeneration is Impaired in Macrophage Colony Stimulating Factor Deficient ... transforming growth factor [TGF]β1 and IL-10) that down-regulate TNF were compared in controls and GdCl-treated rats. In ...
A molecular model of tumour necrosis factor-alpha (TNF), a cytokine responsible for regulating immune cell activity by inducing ... tumour necrosis, tumour necrosis factor - alpha, tumour necrosis factor alpha, tumour necrosis factor-alpha, tumour nercrosis ... Caption: A molecular model of tumour necrosis factor-alpha (TNF), a cytokine responsible for regulating immune cell activity by ... Keywords: atom, cachectin, cachexin, chemistry, cytokine, diagram, factor, human protein, illustration, immunostimulant, model ...
  • Alteration in mucin secretion and/or the expression of mucin genes could be a causative factor in barrier compromise, as secreted polymeric mucin forms a physical barrier between luminal antigens and effector immune cells ( 13 ). (asm.org)
  • 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. (biomedsearch.com)
  • Finally, TNF-alpha augments LPS-induced IL-10 secretion. (jimmunol.org)
  • More importantly, such calcium-mobilizing agents significantly enhanced TNF-alpha-induced IL-6 secretion while RANTES secretion was abrogated. (le.ac.uk)
  • 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. (le.ac.uk)
  • In addition to the stimulation of TNF-alpha secretion by monocytes, okadaic acid appears to modulate TNF-alpha precursor processing, as indicated by a marked increase in the cell-associated 26-kD precursor. (rupress.org)
  • In contrast, there were no significant differences in Mo TNF-alpha secretion between the groups. (ucl.ac.uk)
  • secretion and that a numerically significant subset of mononuclear phagocytes, RFD7, was responsible for more than 80% of TNF-alpha production. (ucl.ac.uk)
  • 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. (unboundmedicine.com)
  • Surprisingly, TNF-alpha was a very potent stimulator of the proliferation of CD34++CD38- cells and was the most potent synergistic factor for the IL-3-induced proliferation of these cells of all cytokines tested (IL-1, IL-6, granulocyte colony-stimulating factor, kit ligand). (rupress.org)
  • Our results showed statistically significant inhibition in DNA damage caused by BV treatment compared to corresponding TNF-alpha/Act D-treated hepatocytes. (unboundmedicine.com)
  • 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. (unboundmedicine.com)
  • 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. (clinicaltrials.gov)
  • 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. (clinicaltrials.gov)
  • 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. (jci.org)
  • The modulation of insulin signaling by TNF-alpha was found to be paralleled by a comparable inhibition of insulin-stimulated glucose transport. (diabetesjournals.org)
  • 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. (diabetesjournals.org)
  • To investigate the effect of systemic or local tumor necrosis factor-alpha (TNF-α) -inhibition with etanercept on experimental autoimmune uveoretinitis (EAU). (arvojournals.org)
  • Since systemic or local TNF-alpha inhibition in the afferent phase improves histological disease, but not in the efferent phase after immunization, we conclude that TNF-α participates mainly in the immunopathology in the induction phase of EAU. (arvojournals.org)
  • 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. (asm.org)
  • 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. (jrheum.org)
  • Interestingly, TNF-alpha-induced interferon regulatory factor (IRF)-1 activation was significantly inhibited by all calcium-mobilizing agents, BK, Thr and Tg. (le.ac.uk)
  • The primary function of TNF-alpha is to recruit other leukocytes to the site of infection and to stimulate their activation. (practo.com)
  • It was also shown that radiotherapy activates ADAM17 in non-small cell lung cancer, which results in shedding of multiple survival factors, growth factor pathway activation, and radiotherapy-induced treatment resistance. (wikipedia.org)
  • We have performed a case-control association study of three TNF-alpha gene polymorphisms in a group of Romanian psoriatic arthritis patients versus ethnically matched controls. (mdpi.com)
  • 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. (molvis.org)
  • Both factors were described based on their ability to kill mouse fibrosarcoma L-929 cells. (wikipedia.org)
  • Also, exogenous IL-2 increases the response of NK cells to hk-LM or to IL-12 and TNF-alpha. (pnas.org)
  • 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. (pnas.org)
  • Tumor Necrosis Factor-producing T-regulatory Cells Are Associated With Severe Liver Injury in Patients With Acute Hepatitis A. Gastroenterology. (umassmed.edu)
  • 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. (aspetjournals.org)
  • We hypothesize that in situations of the hematopoietic stress, TNF-alpha may abrogate the inhibitory effect of ambient TGF-beta in the bone marrow microenvironment to allow primitive stem cells to proliferate and differentiate in response to an increased demand for mature blood cells. (rupress.org)
  • furthermore, the expression pattern of adenocarcinomic cells (A549, H1650, or H1299 cells) was validated under the stimulation with tumor necrosis factor-alpha (TNFα) or dexamethasone (DEX), separately. (springer.com)
  • Cells expressing CD4 secrete TNF-alpha while CD8 cells secrete little or no TNF-alpha. (creativebiomart.net)
  • Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells. (semanticscholar.org)
  • Caco-2 cells were plated onto Transwell microporous filters and treated with TNF-alpha (10 or 100 ng/mL) for 0, 4, 8, 16, or 24 h. (semanticscholar.org)
  • Also, using a salmonid-specific microarray platform (SFA2.0 immunochip) we observed that rtTNF alpha induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling. (stir.ac.uk)
  • Furthermore, the expression of kallikrein, TOP-2, serine protease 23 and ADAM 22, genes that have been postulated to be involved in proteolytic and tissue remodeling processes during ovulation in trout, increases in follicles incubated in the presence of rtTNF alpha. (stir.ac.uk)
  • The use of luciferase-tagged IL-6 and RANTES promoter constructs demonstrated similar effects of Tg on IL-6 and RANTES genes in basal and TNF-alpha-stimulated conditions. (le.ac.uk)
  • 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. (pnas.org)
  • Here, using cultured DH neurons, we have shown that tumor necrosis factorinhibits the total outward potassium current I K and the K Na current predominantly as well as induces a progressive loss of firing accommodation. (dovepress.com)
  • 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. (jci.org)
  • We have determined the plasma concentrations of types 1 and 2 of plasminogen activator inhibitor (PAI-1 and PAI-2), tumor necrosis factor (TNF-alpha) and endotoxin in 47 patients with bacterial infection (22 patients presented with positive blood cultures). (cun.es)
  • 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. (ovid.com)
  • Chlamydia is the most prevalent bacterial sexually transmitted infection (STI) worldwide ( 1 ), and genital chlamydia is associated with significant reproductive morbidity, including tubal factor infertility. (asm.org)
  • As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor alpha (TNF alpha) and other immune factors, are produced and act on the reproductive system. (stir.ac.uk)
  • In 1968, Gale A Granger from the University of California, Irvine , reported a cytotoxic factor produced by lymphocytes and named it lymphotoxin (LT). Credit for this discovery is shared by Nancy H. Ruddle from Yale University , who reported the same activity in a series of back-to-back articles published in the same month. (wikipedia.org)
  • These mutants displayed cytotoxic activities on tumor cell lines in vitro, and exhibited lower systemic toxicity in vivo. (creativebiomart.net)
  • Dexamethasone treatment improves outcome in bacterial meningitis possibly by inhibiting IL-1 beta and TNF alpha. (jci.org)
  • Finally, overexpression of wild-type SAPKbeta was able to overcome the dexamethasone-induced block of TNF-alpha translation. (asm.org)
  • A novel mechanism by which dexamethasone inhibits translation of TNF-alpha is also revealed. (asm.org)
  • 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. (jci.org)
  • 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. (jci.org)
  • We found that TNF-alpha had a major effect on IL-10 mRNA production, inducing a 20- to 120-fold increase over baseline production. (jimmunol.org)
  • 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. (pubmedcentralcanada.ca)
  • Most tissue eosinophils infiltrating nasal polyps were strongly positive for both TNF-alpha and MIP-1 alpha mRNA. (pubmedcentralcanada.ca)
  • 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. (pubmedcentralcanada.ca)
  • 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. (pubmedcentralcanada.ca)
  • 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. (asm.org)
  • It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. (jove.com)
  • b) Increases in pulmonary arterial pressures seen in vivo with TNF-alpha administration are not due to a direct effect. (biomedsearch.com)
  • 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. (mysciencework.com)
  • 1978 ). Morphological factors influencing transepithelial permeability: a model for the resistance of the zonula occludens. (biologists.org)
  • Furthermore, we have demonstrated that the tumor necrosis factormodulation of K Na channels does not occur at the level of SLICK channel gating but arises from possible posttranslational modification. (dovepress.com)
  • Thus, there is evidence that TNF-alpha priming of neutrophils for enhanced NAP-2- or rIL-8-promoted degranulation involves the antagonistic down-modulation of stimulus-induced rises in cAMP. (mysciencework.com)
  • Crespo D, Bonnet E, Roher N, MacKenzie S, Krasnov A, Goetz FW, Bobe J & Planas JV (2010) Cellular and molecular evidence for a role of tumor necrosis factor alpha in the ovulatory mechanism of trout, Reproductive Biology and Endocrinology, 8, Art. (stir.ac.uk)
  • 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). (cdc.gov)
  • Three patients underwent a medical history for TB risk factors before beginning therapy with a TNF-α antagonist. (cdc.gov)
  • 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. (bmj.com)
  • The Effect of Anti-Tumor Necrosis Factor-Alpha Treatment on Muscle Performance and Endurance in Patients With Ankylosing Spondylitis: A Prospective Follow-Up Study. (thefreelibrary.com)
  • 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. (thefreelibrary.com)
  • 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. (thefreelibrary.com)
  • There was a significant increase in PAI-1 and TNF-alpha in patients as compared to controls (p less than 0.0001), whereas no differences for PAI-2 were observed. (cun.es)
  • PAI-1 and TNF-alpha were significantly higher in 18 patients with gram-negative bacteremia as compared to all other patients (p less than 0.0001). (cun.es)
  • We conclude that there is an increase of PAI-1 and TNF-alpha in patients with sepsis, which is not related to the endotoxin concentration. (cun.es)
  • Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1. (pubmedcentralcanada.ca)
  • 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. (ovid.com)
  • 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. (ovid.com)
  • Conclusions There was no decrease in mortality between placebo and TNF-alpha MAb in all infused patients. (ovid.com)
  • In septic shock patients who received TNF-alpha MAb, a significant reduction in mortality was present 3 days after infusion. (ovid.com)
  • 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. (ovid.com)
  • In particular, we wished to assess whether TNF-alpha levels differ between SSc patients with FA (FASSc) and a nonfibrotic group. (ucl.ac.uk)
  • 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. (jci.org)
  • We have previously reported that gamma interferon and tumor necrosis factor alpha (TNF-α) synergistically inhibit HCMV replication in vitro. (asm.org)
  • We investigated regulation of tenascin-C expression by TNF-alpha through nuclear factor-alphaB (NF-kappaB) in OA cartilage in vivo and in vitro. (jrheum.org)
  • In the present study, we have examined for the first time the effects of TNF alpha in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta). (stir.ac.uk)
  • Furthermore, we determined the in vitro effects of rtTNF alpha on follicle contraction and testosterone production in preovulatory brown trout ovarian follicles. (stir.ac.uk)
  • 01) release of TNF-alpha was observed when cultures were first primed with morphine for 24 h and then stimulated with lipopolysaccharide. (aspetjournals.org)