Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that recombinant human interleukin-1 (IL-1) stimulates matrix erosion in bovine nasal cartilage explants (R. J. Smith et al., Inflammation 13, 367-382, 1989). This action of IL-1 is believed to be caused by matrix-degrading neutral proteinases produced by activated chrondrocytes. Accordingly, we investigated the effects of recombinant human interleukin-1 alpha (IL-1 alpha), recombinant human interleukin-1 beta (IL-1 beta), and recombinant human tumor necrosis factor alpha (TNF alpha) on bovine nasal chondrocyte (BNC) responsiveness. IL-1 alpha and IL-1 beta stimulated a time (0-72 hr) and concentration-dependent (0.01-10 ng/ml) production of collagenase, gelatinase, caseinase, and prostaglandin E2 (PGE2) in BNC monolayer cultures. Neutral proteinase and PGE2 production by BNC was also induced by TNF alpha (0.2-200 ng/ml) in a time-dependent (0-72 hr) manner. Recombinant human interleukin-6 (IL-6) caused a concentration-dependent (6-200 ng/ml) potentiation of IL-1-stimulated neutral proteinase and PGE2 production by BNC. However, recombinant human platelet-derived growth factor homodimer BB suppressed BNC responsiveness to IL-1. A recombinant human IL-1 receptor antagonist protein inhibited BNC activation by IL-1 but not TNF alpha.
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PMID:Induction of neutral proteinase and prostanoid production in bovine nasal chondrocytes by interleukin-1 and tumor necrosis factor alpha: modulation of these cellular responses by interleukin-6 and platelet-derived growth factor. 132 6

Minced human tonsils were digested with DNase and collagenase, and lymphoid cell-depleted low density cells were cultured and grown in granulocyte-macrophage-CSF. Large, morphologically homogenous adherent cells with elongated extensions grew continuously in culture. These nonphagocytic cells appear to be related to follicular dendritic cell (FDC) as they do not have properties of monocytic lineage cells or dendritic cells and because, like FDC, 1) they express CD11b, CD14, CD29, CD40, CD54, CD73, CD74, and VCAM-1, and do not express CD11c, CD22, T cell markers, CD18, CD25 and CD45; and 2) they bind human B lymphocytes and B cell lines, but not T lymphocytes by an adhesion blocked in part by mAb to VLA-4 (CD49d). The cultured FDC also augmented B cell proliferation stimulated by anti-mu sera and/or CD40 mAb. Cultured FDC spontaneously produced low levels of IL-6, but did not produce IL-1 alpha or TNF-alpha; however, after treatment with either IFN-gamma or LPS, they produced more IL-6. The expression of CD54 (ICAM-1) was elevated by treating the cultured FDC with either TNF-alpha, IL-1 beta, IFN-gamma or granulocyte-macrophage-CSF; in contrast, IL-4 had no effect on CD54 but rather up-regulated expression of VCAM-1. IFN-gamma, unlike the other cytokines tested, increased expression of a set of markers on cultured FDC (CD54, VCAM-1, and CD14) and converted these class II-negative cells into class II+ cells. The fact that various T cell-derived cytokines have different effects on FDC suggests that the T cell products may influence the manner by which FDC stimulate B cell proliferation and maturation.
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PMID:Cultured human follicular dendritic cells. Growth characteristics and interactions with B lymphocytes. 137 41

The anabolic steroid, stanozolol, is used therapeutically to treat a number of pathological conditions and its clinical effects suggest that it can modulate connective tissue breakdown. The ability of this compound to stimulate prostaglandin E2 (PGE2), collagenase, gelatinase and stromelysin production by human synovial and skin fibroblasts in vitro was examined. The results showed that stanozolol significantly stimulated, in a dose dependent manner, PGE2, collagenase and stromelysin production by skin fibroblasts. However, no stimulation was seen in the synovial cell lines. In contrast, no effect on gelatinase production was seen in either cell type, following exposure to stanozolol. The synovial and skin lines both exhibited a significant stimulation of PGE2 and all three metalloproteinases in response to interleukin-1 beta (IL-1 beta). The anabolic steroids nortestosterone and oxymetholone demonstrated no ability to stimulate PGE2 or collagenase production in either skin or synovial fibroblasts. These results suggest that stanozolol exerts differential effects on skin and synovial fibroblasts in vitro which may enable the elucidation of the mechanism of action of the compound in vivo.
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PMID:The differential responses of human skin and synovial fibroblasts to stanozolol in vitro: production of prostaglandin E2 and matrix metalloproteinases. 152 98

Interleukin 1 receptor antagonist (IL-1ra) has been found in glycosylated form in the urine of febrile patients or of children with rheumatoid arthritis, and in the supernatant of monocytes cultured in the presence of immune complexes. It blocks competitively the binding of IL-1 alpha and beta to their receptors. Produced amongst others by mononuclear cell lines and matured monocytes and alveolar macrophages, it prevents prostaglandin E2 and collagenase production by fibroblasts and synovial cells. In mice, IL-1ra improves survival after lethal endotoxemia. In this study, both natural and recombinant human IL-1ra (rhIL-1ra) were tested in an allogeneic T-cell reaction, and in mitogen- or antigen-induced lymphocyte proliferation. Neither the natural nor the rhIL-1ra blocked T-cell proliferation, but rhIL-1ra abolished the effect of exogenous IL-1 beta. This was not due to a loss of bioactivity of IL-1ra in culture, as the IL-1ra of the supernatant still completely inhibited 125I-IL-1 alpha binding to EL 4-6.1 cells and markedly reduced PGE2 production during antigen presentation. We conclude that IL-1ra alone, even at high concentrations, is not sufficient to block human T-cell proliferation in vitro.
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PMID:Natural and recombinant interleukin 1 receptor antagonist does not inhibit human T-cell proliferation induced by mitogens, soluble antigens or allogeneic determinants. 153 18

Extracorporeal photopheresis (ExP) has been shown to be an efficacious and well-tolerated therapy in the treatment of cutaneous T-cell lymphoma (CTCL) and systemic sclerosis. However, the precise mechanisms of its action have not been defined. Because of a correlation between the development of fever in the early phase of treatment of CTCL and subsequent anti-tumor responses, we examined the production of the proinflammatory, pyrogenic cytokines tumor necrosis factor-alpha (TNF), IL-6, IL-1 alpha, and IL-1 beta before and after ExP. Monocytes were purified from peripheral blood specimens of normal volunteers (n = 4) or from peripheral blood specimens of CTCL (n = 6) or systemic sclerosis (n = 3) patients that were obtained immediately prior to ExP and also directly from the photopheresis unit after ExP, just prior to reinfusion into the patient. Monocytes were then cultured under various conditions for 16 h, after which the culture supernatants were collected and assayed for specific cytokine production. ExP induced a significant increase in the production of TNF (p less than 0.008) and IL-6 (p less than 0.05) as compared to non-ExP-treated cells, whereas no significant differences were observed in IL-1 alpha (p less than 0.5) and IL-1 beta (p less than 0.2) production following ExP. Exposure of monocyte cultures to IFN-gamma (100 U/mL) either before or after ExP further enhanced TNF production by 4 to 28 times. In contrast, incubation with IFN-alpha (100 U/mL) had no significant effect on TNF production. Addition of TNF (500 U/ml) to monocyte cultures obtained prior to ExP resulted in a slight but insignificant increase in TNF production in 2 of 10 cases. However, when monocytes obtained prior to ExP were incubated with 8-methoxypsoralen (8-MOP, 100 ng/ml), exposed to ultraviolet light A (UVA, 2J/cm2), washed, and then incubated with TNF, a significant increase (p less than 0.01) in TNF production was observed in 8 of 10 cases, suggesting that the combination of 8-MOP and UVA may sensitize cells to TNF. Based on studies of endotoxin (LPS)-stimulated production of TNF by monocytes, levels of endotoxin in culture reagents or photopheresis equipment could not account for the increased production of TNF following treatment by ExP. Increased TNF production as a result of ExP may have important implications for treating both CTCL and systemic sclerosis because, in the case of CTCL, it could mediate numerous anti-tumor effects, whereas, in the case of systemic sclerosis, it could suppress collagen synthesis and induce collagenase production.
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PMID:Extracorporeal photochemotherapy induces the production of tumor necrosis factor-alpha by monocytes: implications for the treatment of cutaneous T-cell lymphoma and systemic sclerosis. 156 19

The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-1), prostaglandin E2 (PGE2), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision arthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte proliferation assay to determine IL-1-like activity. IL-1 beta levels in human cell-conditioned media were analyzed by enzyme-linked immunosorbent assay, and PGE2 levels were measured by radioimmunoassay (RIA) using a PGE2 RIA kit (New England Nuclear). Human tissue contained levels of IL-1 beta in the range of 150 to 7,040 pg/mL and PGE2 levels of 82 to 952 ng/mL. The canine specimens contained IL-1-like activity and significant amounts of PGE2 (76 to 1,720 ng/mL). Naproxen decreased PGE2 levels in vitro. This animal model provides the means to investigate the in vivo and in vitro activity of the synovial cells around loose total joint prostheses.
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PMID:Synovium-like tissue from loose joint replacement prosthesis: comparison of human material with a canine model. 160 28

Among the major cytokines present in inflammatory lesions interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) share many biological activities. Since IL-1 alpha, IL-1 beta and TNF alpha have been previously demonstrated to play an important role in connective tissue destruction by stimulating the production of prostaglandin E2 (PGE2) and collagenase, these functions were investigated in the presence or absence of natural human IL-6 (nhIL-6) or recombinant human IL-6 (rhIL-6). IL-6 was found 1 degree to stimulate immunoglobulin A production by the CESS B cell line up to 19 fold without being affected by the presence of IL-1 beta and 2 degrees to stimulate murine thymocytes proliferation up to 2-4 fold, with an increase up to 60-fold in costimulation with either IL-1 alpha or beta. IL-6 alone, even at very high concentrations (up to 200 U/ml and 50 ng/ml), did not induce PGE2 production by fibroblasts and synovial cells. However, IL-1 alpha or beta induced PGE2 production by human dermal fibroblasts and by human synovial cells was inhibited (in 5/8 experiments) up to 62% by addition of IL-6. On the contrary in 2/4 experiments TNF alpha-induced PGE2 production was increased (approximately 2 fold) by the addition of IL-6. IL-1 and TNF alpha-induced collagenase production in synovial cells remained unchanged in the presence of IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of IL-1 inflammatory and immunomodulatory properties by IL-6. 165 82

Synovial fibroblasts freshly isolated from the rheumatoid joint are characterized by their marked connective tissue degradative ability. This phenotype includes the ability to secrete large amounts of the matrix-degrading metalloproteinases, collagenase, and stromelysin. We have found that another aspect of this phenotype is the constitutive expression at both protein and mRNA levels of a 92-kD gelatinolytic metalloproteinase, which is not secreted by normal dermal or lung fibroblasts and is immunologically cross-reactive with a type V collagenase expressed by activated macrophages and neutrophils. Expression of this 92-kD metalloproteinase confers upon the fibroblasts the capacity to degrade collagenase- and stromelysin-resistant interstitial elements, such as collagen types IV, V and XI. In contrast to the 92-kD metalloproteinase, a 68-kD gelatinase (type IV collagenase) was expressed by all fibroblast types studied, indicating that its regulation is distinct from that of the 92-kD gelatinase. To identify what cytokines may be important in the induction of the rheumatoid synovial phenotype, including expression of the 92-kD gelatinase, we exposed normal dermal fibroblasts to a number of cytokines including many known or considered likely to be present in rheumatoid synovial fluid and tissue. Although IL-1 beta, tumor necrosis factor-alpha, lymphotoxin, platelet-derived growth factor, and basic fibroblast growth factor were capable of stimulating fibroblasts to secrete collagenase, only tumor necrosis factor-alpha, lymphotoxin, and IL-1 beta were able to induce expression of the 92-kD gelatinase, demonstrating discordant regulation of the two metalloproteinases. Expression of the 68-kD gelatinase was independent of that of the 92-kD gelatinase, as demonstrated at the protein and mRNA levels. Late passage rheumatoid synovial fibroblasts, which no longer constitutively expressed the 92-kD gelatinase, displayed an accentuated response to IL-1 beta when compared to normal dermal fibroblasts. Thus, in addition to IL-1 beta, tumor necrosis factor-alpha or lymphotoxin may contribute to the expression of a specific rheumatoid synovial phenotype in vivo that is associated with progressive matrix destruction.
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PMID:Constitutive expression of a 92-kD gelatinase (type V collagenase) by rheumatoid synovial fibroblasts and its induction in normal human fibroblasts by inflammatory cytokines. 165 48

The expression of collagenolytic activity by cells represents the rate-limiting step in the turnover of collagen during remodeling. The collagenase gene is transcriptionally activated in normal dermal or rheumatoid synovial fibroblasts by interleukin-1 beta (IL-1 beta), resulting in secretion of trypsin-activatable procollagenase measuring in the range of 2.0-5.0 units/10(6) cells/48 h in the 14C-fibril assay. The addition of interferon-gamma (IFN-gamma; 50-100 units/ml) inhibits the expression of collagenase activity by 45-80% in these cells. The IL-1 beta induction of procollagenase protein was not altered by IFN-gamma, as judged by Western blot analysis using a monoclonal antibody to collagenase and by gelatin zymography, and procollagenase mRNA was also unaltered, as assessed by Northern blot analysis. Because collagenolytic activity is also controlled by the quantity of tissue inhibitor of metalloproteinases present, its expression was examined by Western blot analysis using a polyclonal antibody to tissue inhibitor of metalloproteinases and by reverse gelatin zymography. Tissue inhibitor of metalloproteinase protein was found to be unaltered or slightly less abundant in conditioned media from cultures treated with IL-1 beta and IFN-gamma when compared with that from cultures treated with IL-1 beta alone. However, the expression of the metalloproteinase activator of procollagenase, stromelysin, was found to be significantly inhibited by the addition of IFN-gamma. Addition of purified activated stromelysin to these conditioned media completely reconstituted collagenolytic activity. These observations demonstrate in an intact system that stromelysin is a specific activator necessary for the development of collagenolytic activity. Despite stromelysin's lack of catalytic activity against collagen, its expression can serve as a control point in the regulation of collagenolysis.
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PMID:Stromelysin expression regulates collagenase activation in human fibroblasts. Dissociable control of two metalloproteinases by interferon-gamma. 166 Apr 74

Aminophenyl mercuric acetate (APMA)-activated collagenase (C) (60 U/ml) obtained from in vitro cultures of human skin fibroblasts or recombinant interleukin-1 beta (IL-1 beta) (200 U/ml) was infused continuously for 7 days into the rabbit knee synovial space by means of an implanted Alzet osmotic pump. In stability studies in vitro, activated C or IL-1 incubated for 7 days at 37 degrees C, showed no significant loss of biological activity. Alterations in knee cartilage morphology and proteoglycan (PG) content were determined histologically, and the incidence of cartilage damage calculated. C or IL-1 vehicles infused for 7 days, caused no damage. Incidences of damage for C or IL-1 (n = 8-9), respectively, were as follows: loss PG: 88% and 100%; chondrocyte disorganization and loss, 50% and 78%, fissures and or fraying, 25% and 78%; and convergence of inflammatory cells, 25% and 66%. These results confirm the important role of C and IL-1 in cartilage damage.
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PMID:Rapid induction of early osteoarthritic-like lesions in the rabbit knee by continuous intra-articular infusion of mammalian collagenase or interleukin-1. 166 94


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