Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eicosanoids, lymphokines, and free radicals are known to participate in the pathogenesis of inflammation. Tumour necrosis factor (TNF), interleukin-1 and 6 (IL-1 and IL-6) and colony stimulating factor -1 (CSF-1) are secreted mainly by activated macrophages, whereas T-cells secrete IL-2, IL-3, IL-4 and interferon-gamma (IFN-gamma). In addition, activated macrophages and lymphocytes can also produce eicosanoids and free radicals which have potent pro-inflammatory actions. Eicosanoids, lymphokines, and free radicals can modulate the immune response, cell proliferation, stimulate collagenase and proteases secretion and induce bone resorption; events which are known to be associated with various collagen vascular diseases. On the other hand transforming growth factor-beta (TGF-beta) produced by synovial tissue, platelets and lymphocytes can inhibit collagenase production, suppress T-cell and NK-cell proliferation and activation and block free radical generation and seems to be of benefit in rheumatoid arthritis. Drugs such as cyclosporine, 1,25,dihydroxycholecalciferol and pentoxyfylline can block lymphokine and TNF production and thus, may inhibit the inflammatory process. Essential fatty acids, the precursors of eicosanoids, are suppressors of T-cell proliferation, IL-1, IL-2 and TNF production and have been shown to be of benefit in rheumatoid arthritis, systemic lupus erythematosus and glomerulonephritis. Thus, the interactions between essential fatty acids, eicosanoids, lymphokines, TGF-beta and free radicals suggest that new therapeutic strategies can be devised to modify the course of collagen vascular diseases.
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PMID:Interaction(s) between essential fatty acids, eicosanoids, cytokines, growth factors and free radicals: relevance to new therapeutic strategies in rheumatoid arthritis and other collagen vascular diseases. 172 26

Tumour necrosis factor-alpha (TNF-alpha) is secreted by macrophages in response to inflammation, infection and cancer. Sublethal doses of recombinant TNF-alpha to rats causes cachexia, anaemia and inflammation. TNF-alpha plays a major part in tissue inflammation and remodelling by stimulating production of collagenase. Cellular responses to TNF-alpha are initiated by binding to high-affinity cell surface receptors. TNF-alpha then profoundly affects gene regulation, stimulating the fos, myc, interleukin-1 and interleukin-6 genes and inhibiting the type I collagen gene. Here we demonstrate that TNF-alpha also stimulates collagenase gene transcription; this stimulation is mediated by an element of the gene that is responsive to the transcription factor AP-1, the major component of which (jun/AP-1) is encoded by the jun gene; and that TNF-alpha stimulates prolonged activation of jun gene expression. This prolonged induction of jun contrasts with its transient activation by the phorbol ester TPA and provides a physiological example of the ability of jun/AP-1 to stimulate its own transcription. This may be a key mechanism for mediating at least some of the biological effects of TNF-alpha.
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PMID:Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha. 253 68

Human decidua contains resident decidual cells alongside a population of bone marrow-derived cells, among which macrophages and large granular lymphocytes are most abundant. We hypothesized that soluble effectors produced by bone marrow-derived cells may modulate the function of the decidual cells. To investigate this, a cell purification protocol was devised that involved digestion of first-trimester decidua with collagenase and hyaluronidase to produce a mixed stromal cell suspension from which the bone marrow-derived cells were removed using immunomagnetic beads coated with anti-CD45. The resulting stromal cells were maintained in culture in the presence of progesterone and were found to produce PRL. The effect of a panel of cytokines on PRL production was examined. Tumor necrosis factors-alpha and -beta had a dose-dependent inhibitory effect, and tumor necrosis factor receptors were identified on the cells. Interleukin 1 alpha and 1 beta, platelet-derived growth factor, and transforming growth factor-beta 1 were also found to inhibit PRL production, and platelet-derived growth factor and transforming growth factor-beta 1 stimulated cell proliferation. These findings suggest an interaction between the immune and endocrine systems in regulating the maternal environment of early pregnancy.
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PMID:Comment: effect of cytokines on prolactin production by human decidual stromal cells in culture: studies using cells freed of bone marrow-derived contaminants. 798 96

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10.
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PMID:Increased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease. 1079 71

Tumour necrosis factor-alpha (TNF-alpha) was able to promote collagen breakdown from bovine cartilage in explant culture. This release was dependent upon matrix metalloproteinases (MMPs) and could be prevented by transforming growth factor-beta1 (TGF-beta1) or insulin-like growth factor-1. Both growth factors reduced the expression and secretion of collagenase enzymes, and TGF-beta1 induced tissue inhibitor of metalloproteinase production. This study shows for the first time that these anabolic growth factors can protect cartilage against TNF-alpha-induced destruction.
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PMID:Modulation of the expression of matrix metalloproteinase and tissue inhibitors of metalloproteinases by TGF-beta1 and IGF-1 in primary human articular and bovine nasal chondrocytes stimulated with TNF-alpha. 1166 84

An inflammatory response occurs during cardiac surgery involving cardiopulmonary bypass. Matrix metalloproteinase-9 is an enzyme involved in cytokine processing and leucocyte extravasation. It is secreted as a pro-enzyme in response to several inflammatory mediators and is inhibited by endogenous tissue inhibitor of metalloproteinase-1. The interaction between matrix metalloproteinase-9 and its inhibitor during cardiopulmonary bypass is not known. We measured tumour necrosis factor alpha, and matrix metalloproteinase-9 and its inhibitor using enzyme immunoassay at three time points in 20 patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass. Tumour necrosis factor and matrix metalloproteinase concentrations increased in all patients during bypass (both p < 0.0001), whereas the inhibitor in contrast, decreased (p < 0.0001). We conclude that matrix metalloproteinase-9 is released as part of the inflammatory response during cardiac surgery. Levels of the endogenous inhibitor of metalloproteinase, however, show a different pattern of release, suggesting independent regulation.
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PMID:Matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and tumour necrosis factor alpha release during cardiopulmonary bypass. 1205 24

Tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMPs) play an important role in the pathogenesis of rheumatoid arthritis (RA). The present study was conducted to investigate whether the serum level of TNF-alpha is correlated with MMPs and tissue inhibitors of metalloproteinases (TIMPs) in RA patients. Serum concentrations of TNF-alpha, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were measured by ELISA in 34 patients with RA. We found the TNF-alpha to correlate with MMP-1, MMP-3, MMP-9 and total measured MMPs serum concentrations (p < 0.05 for all comparisons). Furthermore, serum TNF-alpha, MMP-1 MMP-3, MMP-9 and TIMP-1 levels correlated with markers of disease activity such as the erythrocyte sedimentation rate, C reactive protein level and the number of swollen joints. No associations were observed between TNF-alpha and TIMPs serum concentrations. Our results support the concept of the regulation of the MMPs synthesis by cytokines such as TNF-alpha. We conclude that the measurement of the serum TNF-alpha, MMPs and TIMP-1 concentrations may be useful in the assessment of RA activity.
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PMID:[Correlation between tumor necrosis factor alpha and matrix metalloproteinases levels in serum of patients with rheumatic arthritis]. 1293 14