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.Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.Arginine: An essential amino acid that is physiologically active in the L-form.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.Cystatin A: A cytastin subtype found at high levels in the SKIN and in BLOOD CELLS. Cystatin A incorporates into the cornified cell envelope of stratified squamous epithelial cells and may play a role in bacteriostatic properties of skin.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.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.Rationalization: A defense mechanism operating unconsciously, in which the individual attempts to justify or make consciously tolerable, by plausible means, feelings, behavior, and motives that would otherwise be intolerable.Mice, Inbred C57BLAmidohydrolasesThrombospondin 1: An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis.Cystatins: A homologous group of endogenous CYSTEINE PROTEINASE INHIBITORS. The cystatins inhibit most CYSTEINE ENDOPEPTIDASES such as PAPAIN, and other peptidases which have a sulfhydryl group at the active site.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.Gene 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Endostatins: Angiostatic proteins that are formed from proteolytic cleavage of COLLAGEN TYPE XVIII.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.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.Tissue Inhibitor of Metalloproteinase-3: A member of the family of tissue inhibitor of metalloproteinases. Mutations of the gene for TIMP3 PROTEIN causes Sorsby fundus dystrophy.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Tissue Inhibitor of Metalloproteinases: A family of secreted protease inhibitory proteins that regulates the activity of SECRETED MATRIX METALLOENDOPEPTIDASES. They play an important role in modulating the proteolysis of EXTRACELLULAR MATRIX, most notably during tissue remodeling and inflammatory processes.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.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Collagen Type XVIII: A non-fibrillar collagen found in BASEMENT MEMBRANE. The C-terminal end of the alpha1 chain of collagen type XVIII contains the ENDOSTATIN peptide, which can be released by proteolytic cleavage.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.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.Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.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.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.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.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.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.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.Tissue Inhibitor of Metalloproteinase-1: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a N-glycosylated protein, molecular weight 28 kD, produced by a vast range of cell types and found in a variety of tissues and body fluids. It has been shown to suppress metastasis and inhibit tumor invasion in vitro.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.Cystatin B: An intracellular cystatin subtype that is found in a broad variety of cell types. It is a cytosolic enzyme inhibitor that protects the cell against the proteolytic action of lysosomal enzymes such as CATHEPSINS.Tissue Inhibitor of Metalloproteinase-2: A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a 21-kDa nonglycosylated protein found in tissue fluid and is secreted as a complex with progelatinase A by human fibroblast and uncomplexed from alveolar macrophages. An overexpression of TIMP-2 has been shown to inhibit invasive and metastatic activity of tumor cells and decrease tumor growth in vivo.Cathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.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.Matrix Metalloproteinases: A family of zinc-dependent metalloendopeptidases that is involved in the degradation of EXTRACELLULAR MATRIX components.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.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.HemopexinCell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Platelet Factor 4: A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Serpins: A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.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.Angiogenesis Inhibitors: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.Kinetics: The rate dynamics in chemical or physical systems.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cell Line, Tumor: A cell line derived from cultured tumor cells.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Metalloproteases: Proteases which use a metal, normally ZINC, in the catalytic mechanism. This group of enzymes is inactivated by metal CHELATORS.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.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Proteinase Inhibitory Proteins, Secretory: Peptides and proteins found in BODILY SECRETIONS and BODY FLUIDS that are PROTEASE INHIBITORS. They play a role in INFLAMMATION, tissue repair and innate immunity (IMMUNITY, INNATE) by inhibiting endogenous proteinases such as those produced by LEUKOCYTES and exogenous proteases such as those produced by invading microorganisms.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.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.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.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.Matrix Metalloproteinase Inhibitors: Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES.Matrix Metalloproteinase 2: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Angiostatins: Circulating 38-kDa proteins that are internal peptide fragments of PLASMINOGEN. The name derives from the fact that they are potent ANGIOGENESIS INHIBITORS. Angiostatins contain four KRINGLE DOMAINS which are associated with their potent angiostatic activity.Thrombospondins: A family of related, adhesive glycoproteins which are synthesized, secreted, and incorporated into the extracellular matrix of a variety of cells, including alpha granules of platelets following thrombin activation and endothelial cells. They interact with a number of BLOOD COAGULATION FACTORS and anticoagulant factors. Five distinct forms have been identified, thrombospondin 1, -2, -3, -4, and cartilage oligomeric matrix protein (COMP). They are involved in cell adhesion, platelet aggregation, cell proliferation, angiogenesis, tumor metastasis, VASCULAR SMOOTH MUSCLE growth, and tissue repair.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.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Mice, Inbred BALB CSerine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Cystatin C: An extracellular cystatin subtype that is abundantly expressed in bodily fluids. It may play a role in the inhibition of interstitial CYSTEINE PROTEASES.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.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Matrix Metalloproteinase 9: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.Collagen Type IV: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.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.X-Linked Inhibitor of Apoptosis Protein: An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.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.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.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.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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.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.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.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Th2 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.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.Leukocyte Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.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.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.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.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.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)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)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.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.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.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Th1 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.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.)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.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.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.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.Aorta: The main trunk of the systemic arteries.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Adenoviridae: A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.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.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.CASP8 and FADD-Like Apoptosis Regulating Protein: An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Vascular Endothelial Growth Factor A: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.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.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.Oligopeptides: Peptides composed of between two and twelve amino acids.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.Interleukin-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.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.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.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.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Infant, Newborn: An infant during the first month after birth.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Nitric Oxide Synthase Type III: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Interleukin-13: A cytokine synthesized by T-LYMPHOCYTES that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature B-LYMPHOCYTES. It appears to play a role in regulating inflammatory and immune responses.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.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).Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.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.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.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.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Cell Adhesion: Adherence of cells to surfaces or to other cells.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.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Rats, 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. This also includes animals with a long history of closed colony breeding.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.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.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.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.Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.Interleukin-17: A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.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.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).Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.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.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.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.Smoking: Inhaling and exhaling the smoke of burning TOBACCO.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
... and Nuclear factor kappa B. It has also been shown in lab studies to upregulate glutathione, an endogenous antioxidant. Fisetin ... Fisetin, like some other flavonoids, has been found in lab studies to be a topoisomerase inhibitor, which may turn out to be a ... In studies conducted on cells in a laboratory, fisetin inhibits the activity of several pro-inflammatory cytokines, including ... These transcription factors continue to be studied in plant model organisms such as maize and Arabidopsis. The environment of ...
... and by endogenous inhibitors known as tissue inhibitors of metalloproteases (TIMPs). The role of matrix metalloproteases and ... Many cytokines and growth factors are synthesized as membrane bound proforms which undergo proteolytic shedding for activation ... Several growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are trapped ... Hepatocyte growth factor (HGF), an angiogenesis promoting growth factor, is activated by HGF activation factor, a serine ...
The activity of cathepsin S is tightly regulated by its endogenous inhibitor, cystatin C, which also has a role in antigen ... The expression of cathepsin S can be triggered by proinflammatory factors secreted by tumor cells. In tumorogenesis, cathepsin ... proinflammatory cytokines and neutrophils. In vitro, cathepsin S retains some enzyme activity in the presence of 3M urea. ... The list of commercial inhibitors also includes paecilopeptin (acetyl-Leu-Val-CHO) and some others. Cathepsin S has been shown ...
... and GSH inhibitor (e.g. PEITC, buthionine sulfoximine (BSO)). The result is an overall increase in endogenous ROS, which when ... ROS then activate various transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB ... ROS induces chronic inflammation by the induction of COX-2, inflammatory cytokines (TNFα, interleukin 1 (IL-1), IL-6), ... The production of ROS is strongly influenced by stress factor responses in the plant, these factors that increase ROS ...
For example, cytokines and cytokine receptor inhibitors affect cognitive and emotional processes. Recent evidence suggests that ... Immune cells and neuroimmune molecules such as cytokines, chemokines, and growth factors modulate brain function through ... sensorimotor functions through epigenetic reprogramming of endogenous regional neural stem cells". Understanding epigenetic ... These three classes include DNA methylation inhibitors, HDAC inhibitors, and RNA-based approaches. DNA methylation inhibitors ...
Menten P, Wuyts A, Van Damme J (Dec 2002). "Macrophage inflammatory protein-1". Cytokine & Growth Factor Reviews. 13 (6): 455- ... in contrast to these two endogenous pyrogens, the fever induced by MIP-1 is not inhibited by the cyclooxygenase inhibitor ... CCL3 is a cytokine belonging to the CC chemokine family that is involved in the acute inflammatory state in the recruitment and ... Joseph AM, Kumar M, Mitra D (Jan 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): ...
... endogenous pyrogen (EP), and proteolysis-inducing factor (PIF). IL-1α is a unique member in the cytokine family in the sense ... IL-1α inhibitors are being developed to interrupt those processes and treat diseases. IL-1α is produced mainly by activated ... IL-1α is also known as fibroblast-activating factor (FAF), lymphocyte-activating factor (LAF), B-cell-activating factor (BAF), ... Arend WP (2003). "The balance between IL-1 and IL-1Ra in disease". Cytokine & Growth Factor Reviews. 13 (4-5): 323-40. doi: ...
... of the tubular architecture by both myofibroblast buildup and monocyte infiltration Because endogenous BMP-7 is an inhibitor of ... 2008). "A new model for growth factor activation: type II receptors compete with the prodomain for BMP-7". J. Mol. Biol. 381 (4 ... Gould SE, Day M, Jones SS, Dorai H (2002). "BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal ... On a molecular level, BMP-7 represses inflammation by knocking down the expression of several pro-inflammatory cytokines ...
... endogenous - endoscopy - endotoxin - endpoint - enteric - enteritis - entry inhibitors - Env - envelope - enzyme - enzyme- ... granulocyte macrophage-colony stimulating factor (GM-CSF) - granulocyte-colony stimulating factor (G-CSF) - granulocytopenia ... cytokines - cytomegalovirus (CMV) - Cytomegalovirus retinitis - cytopenia - cytotoxic - cytotoxic T lymphocyte (CTL) DAIDS - ... host factors - HPTN - HPV - HRSA - HTLV-I - HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) - HTLV-II - ...
RORγt inhibitors are under development for the treatment of autoimmune diseases such as psoriasis and rheumatoid arthritis. The ... The transcription factor is essential for lymphoid organogenesis, in particular lymph nodes and Peyer's patches, but not the ... Abrogation of the gene's activity generally increases type 2 cytokines and may make mice more vulnerable to oxazolone-induced ... Various oxysterols and in particular the cholesterol percursor desmosterol is claimed to be the endogenous activator of RORγ. ...
The IκBα (inhibitor of kappa B) protein inactivates the NF-κB transcription factor by masking the nuclear localization signals ... or the release of pro-inflammatory cytokines such as tumor necrosis factor (TNF) or interleukin-1 (IL-1). Following immune cell ... though IKK-α phosphorylation occurs concurrently in endogenous systems. Recruitment of IKK kinases by the regulatory domains of ... IκB kinase activity is essential for activation of members of the nuclear factor-kB (NF-κB) family of transcription factors, ...
He found that among the cytokines, interleukin 1b mediates the endogenous release of prostaglandins and IL-8 is responsible for ... This factor was named bradykinin potentiating factor, BPF. In 1968, with the collaboration of Dr. Lewis Joel Greene, from the ... the ACE inhibitors. Ferreira received his M.D. from the Faculty of Medicine of Ribeirão Preto of the University of São Paulo ( ... His group made a relevant contribution to the role of bradykinin and of cytokines in the development of inflammatory ...
Finally, it was shown that, when endogenous NF-κB is induced by TNFα (tumour necrosis factor α) treatment, HIF-1α levels also ... As a consequence, alterations in growth factor, chemokine, cytokine, and ROS balance occur within the cellular milieu that in ... an Orally Active Pan-Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase 1-3 (HIF PHD1-3) for the Treatment of Anemia". ... Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular ...
3-Amino-1,2,4-triazole (3-AT) for example, is a competitive inhibitor of the HIS3-gene product and may be used to titrate the ... Here, a bait protein is fused to a kinase-containing portion of TYK2 and a prey is coupled to a gp130 cytokine receptor ... The premise behind the test is the activation of downstream reporter gene(s) by the binding of a transcription factor onto an ... For example, S. cerevisiae possesses no endogenous tyrosine kinase. If an investigation involves a protein that requires ...
Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H (2009). "A new role for FGF2 as an endogenous inhibitor of anxiety". J. ... Angiogenesis Anxiety disorders Cytokine Fibroblast growth factor Growth factor Proteases in angiogenesis Receptor (biochemistry ... Basic fibroblast growth factor, also known as bFGF, FGF2 or FGF-β, is a member of the fibroblast growth factor family. In ... Ribatti D, Vacca A, Rusnati M, Presta M (2007). "The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and ...
Liu JO (Nov 2003). "Endogenous protein inhibitors of calcineurin". Biochemical and Biophysical Research Communications. 311 (4 ... Esau C, Boes M, Youn HD, Tatterson L, Liu JO, Chen J (Nov 2001). "Deletion of calcineurin and myocyte enhancer factor 2 (MEF2) ... binding domain of Cabin1 results in enhanced cytokine gene expression in T cells". The Journal of Experimental Medicine. 194 ( ... Youn HD, Grozinger CM, Liu JO (Jul 2000). "Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone ...
Cytokine & Growth Factor Reviews. 17 (6): 501-19. doi:10.1016/j.cytogfr.2006.09.009. PMID 17084101. He HQ, Liao D, Wang ZG, ... and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors". The Journal ... "Identification and characterization of an endogenous chemotactic ligand specific for FPRL2". The Journal of Experimental ... to form a cluster which also includes the genes for another G protein-coupled chemotactic factor receptor, the C5a receptor ( ...
These cytokines increase the expression of adhesion factors on endothelial cells to enable transmigration (also called ... patterns of structure and sequence in the kunitz inhibitors interleukins-1β and 1α and fibroblast growth factors". Journal of ... The endogenous IL-1 receptor antagonist (IL-1Ra), also known as anakinra, was tried in clinical trials to lessen systemic ... IL-1 family is a group of 11 cytokines, which induces a complex network of proinflammatory cytokines and via expression of ...
... are a family of functionally and structurally related proteins that serve as endogenous inhibitors of programmed cell death ( ... crmA, or cytokine response modifier A, is a cowpox serpin that inhibits caspases 1, 6 and 8, forming complexes with these ... Like any regulated process, apoptosis is subject to either activation or inhibition by a variety of chemical factors. Apoptosis ... Some of these inhibitors include the Bcl-2 family, viral inhibitor crmA, and IAP's. The Bcl-2 family of proteins can either ...
These insights into the role of DDAH in degrading endogenous inhibitors of NOS, and thereby maintaining vascular NO production ... By oxidizing a sulfhydryl moiety critical for DDAH activity, homocysteine and other risk factors cause ADMA to accumulate and ... inflammatory cytokines, hyperhomocysteinemia, hyperglycemia and infectious agents. Each of these insults attenuates DDAH ... Homocysteine (a putative cardiovascular risk factor) mounts an oxidative attack on DDAH to form a mixed disulfide, inactivating ...
Cytokine Growth Factor Rev. 13 (2): 95-109. doi:10.1016/S1359-6101(01)00038-7. PMID 11900986.. ... Wheelock, EF, Interferon-like virus inhibitor induced in human leukocytes by phytohemagglutinin. Science 149, 310-311, 1965. It ... Cytokine Growth Factor Rev. 13 (6): 441-54. doi:10.1016/S1359-6101(02)00044-8. PMID 12401479.. ... cytokine activity. • protein binding. Cellular component. • extracellular region. • external side of plasma membrane. • ...
... cytokines and growth factors from surrounding connective tissues and active skeletal muscles. Notably, HGF, a cytokine, is ... Increased levels of myostatin up-regulate a cyclin-dependent kinase inhibitor called p21 and thereby inhibit the ... hematopoietic stem cells have all been shown to be able to contribute to muscle repair in a similar manner to the endogenous ... Myocyte nuclear factor (MNF), and c-met proto-oncogene (receptor for hepatocyte growth factor (HGF)) are less commonly used ...
Roles of endogenous cytokines in health and diseaseEdit. Cytokines are often involved in several developmental processes during ... Ogawa described the early acting growth factors,intermediate acting growth factors and late acting growth factors.[9] ... Wheelock EF (July 1965). "Interferon-Like Virus-Inhibitor Induced in Human Leukocytes by Phytohemagglutinin". Science. 149 ( ... these last two factors can vary by cell type. Cytokines are characterized by considerable redundancy, in that many cytokines ...
"Cytokine & Growth Factor Reviews. 26 (4): 389-403. doi:10.1016/j.cytogfr.2015.06.001. PMC 4526340. PMID 26119834.. ... Classes of medications, known as HDAC inhibitors and DNA methyltransferase inhibitors, can re-regulate the epigenetic signaling ... Such exogenous and endogenous sources of DNA damage are indicated in the boxes at the top of the figure in this section. The ... "Cytokine & Growth Factor Reviews. 21 (1): 11-9. doi:10.1016/j.cytogfr.2009.11.005. PMC 2834864. PMID 20018552.. ...
... vascular endothelial growth factor) by epidermal substitutes and tissue remodeling factors (tissue inhibitor of ... The secretion of proinflammatory cytokines (IL-1alpha, TNF-alpha), chemokine/mitogen (CCL5) and angiogenic factor ( ... Endogenous defense mechanisms provide protection of the skin from damages induced by UV. UV exposure which would lead to an ... and Growth factors and cytokines. Lastly, tertiary prevention is the treatment of an existing symptomatic disease process to ...
... it has been proposed that cytokines and neurotropic factors can induce NK-1. Also, SP can induce the cytokines that are capable ... The endogenous receptor for substance P is neurokinin 1 receptor (NK1-receptor, NK1R).[8] It belongs to the tachykinin receptor ... "Inhibitor of apoptosis proteins (IAPs) and their antagonists regulate spontaneous and tumor necrosis factor (TNF)-induced ... and cytokine expression,[58] Reciprocally, cytokines may induce expression of SP and its NK1R.[59][60] In this sense, for ...
As a result, rho GTPase function inhibitors are useful in treating or preventing conditions that result from the abnormally low ... In the instant invention, rho GTPase function inhibitors are found to upregulate endothelial cell Nitric Oxide Synthase ... A use for rho GTPase function inhibitors is provided. ... For example, the cytokines TNF-a and IL-1 are thought to be ... Rho GTPase-specific guanine nucleotide exchange factor inhibitors include chemicals, antisense nucleic acids, antibodies, ...
... the downstream transcription factor IRF4, and the cytokine-signaling inhibitor SOCS-3. Thus, aside from its potential to ... we also observed the up-regulation of both endogenous Notch1 and Notch3 receptors. Notch activity also induced a notable number ... These gene products act at multiple levels of cytokine signaling and include the cytokine TGFα, the high-affinity IL-2Rα CD25, ... and the serine protease inhibitor, serpin1b. This cluster may include genes that require thymic stromal cell factors in ...
Treatment with an inhibitor of MAPK phosphorylation mimics the effects of methylprednisolone on RGC survival. To test whether ... Thus, the neurodegenerative aspect of MS pathology seems to be an imperative preconditional factor for serious unwanted side ... modulating the expression of cytokines (Wandinger et al., 1998) or inhibiting leukocyte migration (Gelati et al., 2002). ... PD 98059 is a selective and cell-permeable inhibitor of the single upstream kinase MEK, which in turn phosphorylates and ...
Kone77 demonstrated that treating mesangial cells with DNA methylation inhibitors augmented cytokine induction of endogenous NO ... Given that similar factors regulate NOS 3 expression in the inner medullary collecting duct and thick ascending limb, high salt ... Localization of protein inhibitor of neuronal nitric oxide synthase in rat kidney. Am J Physiol Renal Fluid Electrol Physiol. ... Activity of all 3 NOS isoforms is modulated by protein-protein interactions.41 Protein inhibitor of neuronal NOS (PIN),42,43⇓ ...
... inhibitor U0126 efficiently blocks TPA-induced IkappaBalpha processing in these cells. However, in U2OS cells, the cytokine- ... since both the PKC inhibitor GF109203 and a catalytically inactive PKC-alpha mutant inhibit activation of endogenous IKK by TPA ... Inactive nuclear factor kappaB (NF-kappaB) complexes are retained in the cytoplasm by binding to inhibitory proteins, such as ... but not by tumor necrosis factor-alpha (TNF-alpha). We conclude that IKK is an integrator of TNF-alpha and TPA signal ...
HDAC inhibitors blunt DC allostimulatory capacity and cytokine secretion. The effect of HDAC inhibitors on DC immunostimulatory ... HDAC inhibitors have been reported to cause a down-regulation of the hematopoietic transcription factor PU.1, which contributes ... Importantly, IRFs are activated not only by TLR triggering but also by endogenous signals, such as CD40L and cytokines. The IFN ... lymphokines, cytokines, chemokines, and growth factors. Histone deacetylases (HDAC) are enzymes that, in concert with their ...
The effect of cytokine inhibitors on NMDAR subunit NR1 phosphorylation in the RVM and behavioral hyperalgesia and allodynia at ... There were prolonged elevations of cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) after CCI, and they ... Intra-RVM microinjection of glial inhibitors and neutralization of endogenous TNF-α and IL-1β significantly attenuated CCI- ... We found a prolonged astrocytic reaction and increased expression of cytokines tumor necrosis factor-α (TNF-α) and interleukin- ...
An imbalance in this complex network of cytokines (ie, of proinflammatory cytokines and endogenous cytokine inhibitors) has ... Tissue necrosis factors, interleukins, interferons, and epithelial neutrophil-activating factors are but a few of these ... While certain cytokines stimulate an inflammatory reaction, others inhibit inflammation. Moreover, the same cytokine may have ... For example, a substance known as nerve growth factor (NGF) can cause an increase in the number and the sensitivity of the ...
Endogenous IFN-α/β-mediated inhibition of these cytokines was shown to occur in vivo during infection with LCMV (Figs. 3 and 4 ... Other known inhibitors are transforming growth factor β (TGF-β) and IL-10. Unlike IFN-α/β, TGF-β has been reported to inhibit ... The endogenous virus-induced IFN-α/β effect on IL-12 induction in response to a known inducer of the factor was tested by ... Studies from this laboratory evaluating endogenous expression and function of IL-12 indicate that the factor is differentially ...
In this regard, inhibitors of cytokine expression can markedly downregulate the expression of HIV in an in vitro infection ... We have recently shown that a tightly controlled autocrine loop of endogenous cytokine control of HIV expression exists [25]. ... It seems likely that several factors, such as abnormal cytokine production in the bone marrow and infection of stromal or other ... Hence, the expression of HIV in vivo is probably at least partly modulated by the endogenous cytokine network that is generally ...
... and endogenous sources (including TNF-α and CD40L), as well as reduced cytokine production and immunostimulatory capacity. LPS- ... MyD88 recruits members of the IRAKs and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) to finally activate NF ... NF-κB inhibition is a well-known effect of proteasome inhibitors and is attributed to the impeded degradation of the inhibitor ... Supernatants were collected and stored at -70°C until use for cytokine determination. Cytokine concentrations were measured ...
... both the endogenous activation and exogenous factors-induced activation of STAT3 could be blocked by YL064. Based on these data ... the bone marrow microenvironment confers protection effect to MM cells by direct cell contact or releasing cytokines such as ... In MM cells, STAT3 is aberrant activated by endogenous (e.g., IKK) or exogenous signals (e.g., stromal cells or IL-6) (Fig. 1)5 ... Sinomenine derivative YL064: a novel STAT3 inhibitor with promising anti-myeloma activity. *Yingying Wang1. ,2. , ...
Blood coagulation is processed by coagulation factors. The blood coagulation can be prolonged or stopped when endogenous or ... platelet activating factor, cytokines, bradykinin, fibrin, complement component, eicosanoids, nitric oxide and reactive oxygen ... Marine algae produce a diverse array of secondary metabolites which play a pivotal role as inhibitors of inflammation [97]. ... By the addition of fucoxanthin in a dose-dependent manner, the release of cytokines TNF-α, IL-1β and IL-6 were also reduced [ ...
Significantly, small molecule pan-IAP antagonists that mimic an endogenous inhibitor of the IAPs, called Smac, have ... to sensitize cancer cells to tumor necrosis factor-alpha and to promote autocrine or paracrine production of this cytokine by ... The inhibitor of apoptosis (IAP) family members, defined by the presence of a baculovirus IAP repeat (BIR) protein domain, are ...
1997) Endogenous adenosine curtails lipopolysaccharide-stimulated tumour necrosis factor synthesis. Scand J Immunol 45: 132-139 ... 1995) The specific type IV phosphodiesterase inhibitor rolipram combined with adenosine reduces tumor necrosis factor-a (TNF-. ... The overall cytokine hierarchy remained constant over the 3 independent experiments. Thus the cytokine profile of full T cell ... by a factor of 3, by a factor of 4, by a factor of 5, by a factor of 6, by a factor of 7, by a factor of 8 or by a factor of 9 ...
... and tumor necrosis factor-alpha (TNF alpha) are remarkably pleiotropic neural cytokines/neurotrophic factors that orchestrate ... Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and ... Whether endogenous adult NSPCs secrete functionally relevant growth factors remains unclear. We show that adult hippocampal ... One of the factors that may influence the cytokine secretion profile of a T cell is the antigen-presenting cell (APC). Since ...
Simultaneously, some investigations were also carried out to identify the transcription factors regulating endogenous C/EBP5 ... With the use of a range of commercially available pharmacological inhibitors, our initial investigations led to the ... and to identify the nuclear factors regulating this response. However, unlike endogenous C/EBP5 mRNA and protein expression, ... Additionally, a number of cytokines and other inflammatory mediators modulate the expression/activity of C/EBP8 during the APR ...
inflammatory cytokines decrease CYP450 expression. - liver function. Metabolic Drug Interactions. Drug-Endogenous Interactions ... CYP3A4 inhibitor => increases bioavailability of CYP3A4 substrates. - no effect on hepatic CYP3A4, only enterocyte (GI) CYP3A4) ... act as ligands => bind to transcription factors => increase transcription of CYP genes => induces expression of CYP enzymes. - ... attaches a large endogenous polar compound to make drug more water soluble and easily excretable. - faster than Phase I. - ...
The cytokine vascular endothelial cell growth inhibitor (VEGI; TNFSF15; TL1A) is an endogenous negative regulator of ... On the other hand, angiogenic factors such as vascular endothelial cell growth factor (VEGF) is known to be highly expressed in ... We show here that an imbalance of angiogenesis promoters and inhibitors, namely, the down-regulation of VEGI and up-regulation ...
I/R stimulated the degradation of inhibitor of nuclear factor-κB-α, nuclear translocation of nuclear factor-κB, and up- ... Nuclear factor-κB is essential for activating the transcription of a proinflammatory cascade of cytokines and chemokines to ... 3 NF-κB activation is tightly regulated by its endogenous inhibitor, IκB, which complexes with NF-κB in the cytoplasm. Previous ... Effect of valproic acid (VPA) and zinc protoporphyrin IX (ZnPP) on tumor necrosis factor (TNF)-α and cytokine-induced ...
... is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and ... 77] demonstrated that also FOXO4 was an endogenous inhibitor of NF-κB and a deficiency of FOXO4 could induce colonic ... 29] observed that IL-10 and transforming growth factor-β (TGF-β), two anti-inflammatory cytokines, stimulated a rapid ... Hattori Y, Suzuki K, Hattori S, Kasai K (2006) Metformin inhibits cytokine-induced nuclear factor κB activation via AMP- ...
... migration inhibitory factor). In vitro experiments identify RPS19 as the first endogenous MIF inhibitor by blocking the binding ... with the consequent production and release of profibrotic cytokines and growth factors that drive the fibrotic process. In ... Risk Factors for Poor Treatment Outcomes in Patients with MDR-TB and XDR-TB in China: Retrospective Multi-Center Investigation. ... Transforming growth factor (TGF)-?1 is an important mediator in this process; however, its signaling mechanisms had not been ...
2.2.1. Specific Growth Factors and Small Molecules. Application of various combinations of specific growth factors in ... inhibitor and modulation of Wnt pathway with β-catenin shRNA or chemical Wnt inhibitors (IWR2, IWP4) it is possible to produce ... S. L. Paige, T. Osugi, O. K. Afanasiev, L. Pabon, H. Reinecke, and C. E. Murry, "Endogenous Wnt/beta-catenin signaling is ... cytokine- and xeno-free conditions," Cell Reports, vol. 2, pp. 1448-1460, 2012. View at Google Scholar ...
Plasma concentrations of pro-/anti-inflammatory cytokine IL-6 (Figure 1), anti-inflammatory cytokines IL-10 and IL-1Ra of all ... APC inhibits TNF-alpha production by blocking nuclear factor (NF) kB transcription factor in monocytes [30]. APC has been shown ... APC also inactivates plasminogen activator inhibitor, which results in increased fibrinolysis [18]. ... the major endogenous anticoagulant in man, associate with the development of organ dysfunction in AP [22]. In patients with ...
An imbalance between proinflammatory cytokines and cytokine antagonists or inhibitors may be one factor predisposing to ... Conclusions: An imbalance between proinflammatory cytokines and cytokine antagonists or inhibitors may be one factor ... thus functioning as an inhibitor of IL-1 binding. Endogenous production of IL-1Ra is an important anti-inflammatory mechanism ... Cytokine imbalance in the pathogenesis of rheumatoid arthritis: the role of interleukin-1 receptor antagonist Semin Arthritis ...
  • 1. A method of enhancing an immune response in a host, comprising administering to the host an A.sub.2a receptor antagonist in combination or alternation with a checkpoint inhibitor. (patents.com)
  • The natural inhibitor of IL-1 ( 12 , 13 , 14 ), cloned in 1990 ( 15 ) and renamed the IL-1 receptor antagonist (IL-1ra), stimulated a great deal of interest since it was now possible to specifically block the biological activity of IL-1. (jimmunol.org)
  • By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase (MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. (jneurosci.org)
  • Furthermore, during infections of mice with lymphocytic choriomeningitis virus (LCMV), this treatment revealed a previously undetected early IL-12 and IFN-γ protein expression, and mice deficient in IFN-α/β receptor function, but not control mice, also expressed endogenous LCMV-induced IL-12. (pnas.org)
  • The inhibitor of apoptosis (IAP) family members, defined by the presence of a baculovirus IAP repeat (BIR) protein domain, are key regulators of cytokinesis, apoptosis and signal transduction. (nih.gov)
  • Expression of APP genes is known to be regulated by the CCAAT Enhancer Binding Protein (C/EBP) family of transcription factors, which consists of six members (a-Q. Several studies have implicated C/EBP5 as an important regulator of APP gene transcription during inflammation. (bl.uk)
  • However, unlike endogenous C/EBP5 mRNA and protein expression, both of which were induced by IL-1, the activity of the human C/EBP5 gene promoter was not stimulated by this cytokine, despite being responsive to IL-6 action. (bl.uk)
  • Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. (springer.com)
  • AMPK is activated via allosteric regulation of increased AMP concentration and by the phosphorylation of α subunit (Thr172) via the upstream kinases serine/threonine kinase 11 (LKB1), Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ), and transforming growth factor-β-activated kinase 1. (springer.com)
  • Proinflammatory cytokines upregulate thrombin formation and downregulate the host's antithrombotic mechanisms, in particular the protein C (PC) pathway reviewed in [ 21 ]. (hindawi.com)
  • A restoration of the balance between IL-1Ra and IL-1 in human disease can theoretically be achieved through the administration of recombinant IL-1ra protein, gene therapy with the IL-1Ra complementary DNA, or stimulation of production of endogenous IL-1Ra. (nih.gov)
  • Renal expression of the endogenous chaperones, protein disulphide isomerase (PDI), and 78 kDa glucose-regulated protein (GRP78, also known as binding Ig protein (BiP)), were increased in 4-PBA-treated mice. (portlandpress.com)
  • A mechanism by which the Ras-mitogen-activated protein kinase (MAPK) signaling pathway mediates growth factor-dependent cell survival was characterized. (sciencemag.org)
  • Rsks also are known to phosphorylate the transcription factor CREB (cAMP response element-binding protein) at serine 133. (sciencemag.org)
  • The small guanosine triphosphatase protein Ras is a key mediator of growth factor-dependent cell survival ( 2 ). (sciencemag.org)
  • The results indicated that neutralisation of both IL-1 and TNF-α was needed to achieve a degree of cytokine (IL-6, IL-8, and monocyte chemoattractant protein-1) and matrix metalloproteinase (1, 3, 9, and 13) inhibition, as assessed by enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction (RT-PCR), similar to that observed in CD14 + -depleted cultures. (biomedcentral.com)
  • We recently generated IL-4 gene knockin bicistronic reporter mice that allow the faithful tracking of IL-4 expression using an enhanced green fluorescent protein (eGFP) reporter while preserving intact endogenous IL-4 ( 10 ). (rupress.org)
  • S100A8/A9-mediated cytokine production was suppressed significantly by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely by nuclear factor kappa B (NF-κB) inhibitors. (biomedcentral.com)
  • The nuclear protein DEK is an endogenous DNA-binding chromatin factor regulating hematopoiesis. (jci.org)
  • We describe two procedures: (i) one approach is used to analyze MMP-9-TIMP-1 interactions using recombinant human MMP-9 with its corresponding recombinant human TIMP-1 inhibitor and (ii) the second approach is used to analyze native or endogenous MMP-9-TIMP-1 protein interactions in samples of human plasma. (frontiersin.org)
  • 1983), could be related to induction of the inhibitor protein. (unu.edu)
  • In moving towards producing a potent TNF inhibitor for use in humans, a fusion protein has been prepared containing the extracellular domain of the human 55 kd TNF receptor linked to the Fc and hinge region of mouse IgG1 heavy chain and expressed in CHO cells (PEPPEL, CRAWFORD and BEUTLER, 1991). (unu.edu)
  • Recent studies have demonstrated that angiogenesis, facilitated via administration of angiogenic growth factors as in recombinant protein therapy 2 3 4 5 6 7 or gene transfer, 8 9 10 may be augmented in animal models of myocardial and limb ischemia. (ahajournals.org)
  • Objective - Because extracellular matrix metalloproteinase inducer (EMMPRIN), a tumor cell-derived protein, induces matrix metalloproteinases (MMPs) in fibroblasts and because MMPs are important in atheroma formation, we investigated if EMMPRIN was expressed in granulocyte/macrophage-colony stimulating factor (GM-CSF)-differentiated human peripheral blood monocytes (HPBM) and macrophage foam cells. (ahajournals.org)
  • Not only are TNF-α and IL-1ß centrally involved in causing joint damage in RA, but these cytokines also exert a powerful influence on whole-body protein and energy metabolism. (jrheum.org)
  • Ligation of IL‐1RI in combination with the IL‐1R accessory protein (IL‐1RAcP) results in activation of MyD88‐toll signaling cascades culminating in MAPK‐ and NF‐κB‐dependent expression of inflammatory cytokines and adhesion molecules. (comprehensivephysiology.com)
  • The protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) were determined by Western blot. (ahajournals.org)
  • 1 The main mechanism of hypoxia-induced angiogenesis involves the rise in hypoxia-inducible factor-1α protein, resulting in increased expression of vascular endothelial growth factor (VEGF), a specific angiogenic factor. (ahajournals.org)
  • Human interferon-inducible Protein 10 is a potent inhibitor of angiogenesis in vivo", J. Exp. (patentgenius.com)
  • Recent work published in BMC Cell Biology describes a fusion protein that combines a peptide previously shown to home in on the gastric cancer vasculature with the anti-tumor cytokine TNF-α, and assesses its potential for gastric cancer therapy. (biomedcentral.com)
  • Apoptotic cell death is significantly promoted in cells expressing JNK but effectively suppressed in cells expressing a dominant-negative JNK1 mutant or JBD a JNK inhibitor protein.34 In agreement with these data we also found that JNK activation is efficiently prevented by the reversible ATP-competitive inhibitor of JNK SP600125 and this perturbation of JNK activation resulted in prevention of DNA fragmentation. (exposed-skin-care.net)
  • Jurkat E6.1 cells (2 × 106 per ml RPMI 1640 medium) were incubated … Discussion There is cumulative evidence that JNK has an essential role in apoptosis induced by UV radiation growth factor withdrawal chemotherapeutic drugs and ceramide.33 34 In this study we could show that JNK activation is also required for apoptosis of human lymphoblastoid Jurkat T cells induced by gal-1. (exposed-skin-care.net)
  • These results suggest that, if endogenous IL-12 is to play a role in viral infections requiring CD8 + T cell responses for defense, the levels of expression would have to be tightly regulated. (pnas.org)
  • There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. (springer.com)
  • These results suggest that, in the osteoarthritis synovium, both inflammatory and destructive responses are dependent largely on macrophages and that these effects are cytokine-driven through a combination of IL-1 and TNF-α. (biomedcentral.com)
  • Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes. (rupress.org)
  • The CXCR4 inhibitor, plerixafor, is a more rapid mobilizer, yet not potent enough when used as a single agent, thus emphasizing the need for faster acting agents with more predictable mobilization responses and fewer side effects. (jci.org)
  • We used a standardized 15 min escalating tidal volume injury maneuver in preterm sheep delivered at 133-134 d gestation to test if inhibitors of IL-8, IL-1, or NF-κB would decrease injury responses. (biomedcentral.com)
  • Cytokines produced during the acute inflammatory insult also actively participate in and shape lung reparative responses (see Fig. (comprehensivephysiology.com)
  • These data demonstrate that Trip-1 can simultaneously modulate responses involving both cytokine and nuclear receptors. (edu.au)
  • 9 The activated endothelial cell upregulates the surface expression of cell adhesion molecules and secretes cytokines, which act to sequester neutrophils in the ischemic zone. (ahajournals.org)
  • To allow for com parisons of enrichment profiles between the epithelial and mesenchymal samples, we normalized pairs of Inhibitors,Modulators,Libraries REs for each histone modification or variant. (parp1inhibitor.com)
  • Taken together, these findings represented a major discovery since, for more than 50 years, investigators had attempted to prove the existence of a substance secreted by leukocytes that was able to induce fever ("leukocytic pyrogen") and the synthesis of hepatic acute phase proteins, alter lymphocyte function ( 6 ), and exert other biological activities, including production of prostaglandin E 2 , collagenases ( 7 ), platelet-activating factor, and NO ( 8 ). (jimmunol.org)
  • Importantly, virtually all the HDAC inhibitors available show some degree of preclinical activity in tumor cell lines and in animal cancer models ( 1 , 2 ). (aacrjournals.org)
  • 13 Blocking NF-κB activation with pyrrolidine dithiocarbamate or the proteasome inhibitor n -Tosyl-Phe-chloromethyl ketone blocked the upregulation of the ICAM-1 gene. (ahajournals.org)
  • the mitochondria are not directly accessible to the full range of substrates and inhibitors, and the complexity of cytoplasmic metabolism must be considered together with the presence of separate pools of adenine nucleotides, nicotinamide nucleotides and calcium in the cytoplasm and mitochondrial matrix. (biochemj.org)
  • BamHI and SalI sites were introduced downstream of the translational stop and upstream of the endogenous polyadenylation site using PCR-mediated mutagenesis, and the mutated fragment was inserted into pgkTK containing herpes simplex thymidine kinase for negative selection ( 11 ). (rupress.org)
  • Studies from this laboratory evaluating endogenous expression and function of IL-12 indicate that the factor is differentially regulated in contrasting viral infections of mice. (pnas.org)