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)

The islet from human fetal pancreas was separated by collagenase type V (0.5 mg/ml) and cultured to observe spontaneous secretion of interleukin-6 (IL-6), its relationship to insulin secretion, regulatory effect of IL-6 on insulin secretion of islets and IL-6 gene expression of human fetal islets. IL-6 was secreted by cultured human fetal islets in vitro and paralleled to their insulin secretion. The MH60.BSF2 cell proliferated by 50 folds when cultured to the supernatant of human fetal islets. RNA dot hybridization with bioting-labelled IL-6 cDNA showed that IL-6 gene expressed on human fetal islets. IL-6 promoted the insulin secretion of islets dose-dependently. The results suggested that IL-6 may be one of the promoting or regulating factors in the insulin secretion of islets.
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PMID:[Interleukin-6 gene expression of human fetal islets and its relation to insulin secretion]. 831 93

In order to understand further the effects of Newcastle-disease-virus(NDV)-modified tumour vaccines we investigated the feasibility of isolating lymphocytes from the site of injection of patients undergoing postoperative active specific immunization (ASI) with autologous NDV-modified tumour cells. Delayed-type-hypersensitivity(DTH)-like reactions from five cancer patients were surgically removed, minced and the tissue particles were digested with collagenase and DNase. Lymphoid cells recovered were expanded in a highly efficient limiting-dilution analysis system optimized for T cell growth [Moretta et al. (1983) J Exp Med 157: 743] and lymphocyte microcultures (clonal probability > 0.8) could be grown for up to 1 year. Analysis of the microcultures for phenotype and function showed that the majority were positive for CD4 (92%) and TCR alpha beta (96%). Concanavalin-A-induced production of interleukin-2 (IL-2), IL-6, interferon gamma and tumour necrosis factor alpha was detected in more than 70% of the microcultures. Lectin-dependent cytotoxicity was only very rarely observed. The general characteristics of the microcultures obtained support the notion of a DTH-like reaction taking place at the site of tumour cell challenge. The possibility of in vitro expansion and cultivation of T lymphocytes from ASI vaccination sites should help to elucidate further the role of these cells in active specific immunization against autologous tumour cells.
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PMID:In vitro expansion and analysis of T lymphocyte microcultures obtained from the vaccination sites of cancer patients undergoing active specific immunization with autologous Newcastle-disease-virus-modified tumour cells. 834 63

It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase, and that such degradation is regulated by metalloproteinase inhibitors (TIMP). Therefore, the balance between collagenase and TIMP is an important factor for tissue destruction in inflammatory joints. In the present study the effects of cytokines on collagenase and TIMP production in chondrocytes as well as the effects of cytokines on TIMP production in connective tissue cells were studied. IL-1 beta inhibited TIMP production in endothelial cells while enhancing TIMP production in synovial cells and chondrocytes. In addition, tumour necrosis factor-alpha (TNF-alpha) significantly inhibited and IL-6 significantly enhanced TIMP production in endothelial cells, synovial cells and chondrocytes. In the chondrocyte supernatant, collagenase activity/TIMP ratio was significantly elevated by the addition of either IL-1 beta or TNF-alpha to the cells, whereas the ratio was significantly decreased by IL-6. These results suggest that the cytokine effects on TIMP production are different among the different cell types, and that either IL-1 beta or TNF-alpha induce cartilage matrix degradation by disrupting the collagenase/TIMP balance, while, on the other hand, IL-6 protects the tissue through an opposite effect.
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PMID:The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells. 840 97

Human vascular endothelial cells (HUVEC) exhibit various immunological functions, i.e. expression of HLA class-II antigens after incubation with IFN-gamma or antigen presenting function. It has also been reported that HUVEC are able to produce IL-1, IL-6, GM-CSF and immunologically active cleavage products of arachidonic acid. In our study we investigated whether various cytokines, namely IL-1, IL-2, IL-6, GM-CSF and IFN-gamma, do alter the proliferative capacity of HUVEC, the production of van Willebrandt factor (vWF) and the expression of MHC class-II antigens. HUVEC were prepared by the collagenase digestion of human umbilical veins. Monolayers of cells were incubated with cytokines in different concentrations for 24 and 48 h. IFN-gamma inhibits the HUVEC [3H]thymidine uptake in a dose-dependent manner. Suppression of proliferation (40.1%) could be observed after 24 h incubation with 100 U IFN-gamma/ml. IL-1 was a more effective inhibitor of HUVEC proliferation (54% at 10 U/ml and 24 h incubation and 48.4% after 48 h) than IFN-gamma. IL-6 and GM-CSF showed an increasing effect on proliferation with 226% and 151% of the control group, respectively. IFN-gamma after an incubation period of 12 h and IL-1 after 24 h reduced the vWF content by about 30%. Bright MHC class-II expression was induced only by IFN-gamma. In conclusion, some of the immunoregulative cytokines might play an important role in the control of HUVEC proliferation.
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PMID:Effects of interleukin-1, -2, -4, -6, interferon-gamma and granulocyte/macrophage colony stimulating factor on human vascular endothelial cells. 850 49

Tissue inhibitor of metalloproteinases (TIMP-1) is a potent inhibitor of activated matrix metalloproteinases (MMP) such as collagenase, stromelysin, and gelatinase, and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells. Since various cytokines and growth factors can modify the production of MMP and TIMP-1, we explored the action of oncostatin M (OM), a unique lymphocyte- and monocyte-derived cytokine, on expression of these proteins. We examined the regulation of TIMP-1 expression in cultured human fibroblasts by cytokines including OM, IL-6, leukemia inhibitory factor (LIF), and IL-1 alpha. When used at levels of 5 to 50 ng/ml, OM, IL-6, LIF, and IL-1 alpha elevated the TIMP-1 expression at the RNA level in fibroblasts of lung or synovial origin. Interestingly, OM stimulation resulted in highest levels of TIMP-1 RNA and protein synthesis. However, unlike IL-1 alpha, the cytokines OM, IL-6, and LIF did not induce MMP or PGE2 release. OM also enhanced TIMP-1 mRNA levels in the H2981 lung carcinoma and HepG2 hepatoma cell lines. The results suggest that OM as well as IL-6 and LIF, other cytokines acting through similar receptor pathways, may act to inhibit net MMP activity by specifically up-regulating TIMP-1 expression. The selective induction of TIMP-1 by OM may be influential in altering matrix destruction in chronic inflammation and tumor metastasis.
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PMID:Selective regulation of metalloproteinase inhibitor (TIMP-1) by oncostatin M in fibroblasts in culture. 851 78

Leg ulcers present a common and recurring problem in older people creating discomfort and distress for the patient and a great cost to the health care services. Cultured keratinocyte grafts have been used by many investigators to stimulate healing of chronic venous ulcers. It has been proposed that they may do this by producing cytokines which modulate the healing process. However, the types and levels of cytokines in the leg ulcer fluid before and during healing are not known. Wound fluid was collected from venous leg ulcers in 18 patients beneath occlusive Tegaderm dressing for 4 to 6 h. The leg ulcers were divided on clinical criteria into 'healing' and 'non-healing'. PDGF-AB, GM-CSF, IL-1 alpha, IL-1 beta, IL-6 and bFGF were measured by ELISA and the levels of IL-1 alpha, IL-1 beta and IL-6 were also measured using biological assays. The effect of leg ulcer wound fluid on fibroblast and keratinocyte proliferation was measured indirectly by 3H-thymidine incorporation and MTT assay. Total protein, albumin levels, fibronectin degrading activity and collagenase activity, both active and latent were measured. No statistically significant differences in the levels of cytokines or collagenase were identified between healing and non-healing leg ulcers in the sample of leg ulcers studied. However, this study does give valuable information concerning the levels of cytokines and collagenase in chronic leg ulcer wound fluid.
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PMID:Cytokine and protease levels in healing and non-healing chronic venous leg ulcers. 860 41

End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFbeta1-expressing CD68+ cells coproduce IL-1beta and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFbeta1+ CD68+ cells places them in the vicinity of IFN-gamma secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFbeta and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFbeta1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFbeta1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.
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PMID:Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis. 883 14

To determine whether lipopolysaccharides (LPS) regulate mouse placental lactogen-I (mPL-I), mPL-II, and mouse GHRF (mGHRF) secretion, mouse placental tissue from days 7, 9, and 12 of pregnancy was dispersed with collagenase and the purified trophoblast cells were cultured in a serum-free medium with or without LPS for 5 days. LPS significantly inhibited mPL-II secretion by cells from days 9 and 12 of pregnancy. However, LPS did not affect mPL-II secretion by cells from day 7 of pregnancy, mPL-I secretion by cells from days 7 and 9 of pregnancy, or mGHRF secretion by cells from day 12 of pregnancy. The inhibitory effect of LPS on mPL-II secretion by cells from day 12 of pregnancy was dose-dependent. Steady-state levels of mPL-II mRNA were significantly reduced by incubation of placental cells from day 12 of pregnancy with LPS. The inhibitory effect of LPS on mPL-II secretion was abolished by the addition of antibodies to IL-1 alpha and IL-6. These findings suggest that LPS selectively inhibit mPL-II secretion, at least partly through increases in IL-1 and IL-6 production, after midpregnancy.
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PMID:Lipopolysaccharides selectively inhibit mouse placental lactogen-II secretion through stimulation of interleukin-1 alpha (IL-1 alpha) and IL-6 production. 888 34

The cytokines are the putative mediators of the catabolic reaction that accompanies infection and trauma. Evidence suggests that their catabolic actions are indirect and potentially mediated through changes in hormonal axis such as the hypothalamo-pituitary-adrenal axis. Insulin-like growth factor I (IGF-I) is a GH-dependent growth factor that regulates the protein metabolism. To determine whether cytokines can directly inhibit the production of IGF-I by the liver, we investigated the regulation of IGF-I gene expression by interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha (10 ng/ml) in a model of rat primary cultured hepatocytes. Hepatocytes were isolated by liver collagenase perfusion and cultured on Matrigel 48 h before experiments. Each experiment was performed in at least three different animals. In the absence of GH, IL-1 beta and TNF-alpha did not affect the IGF-I messenger RNA (mRNA) basal levels, whereas IL-6 increased it by a factor of 2.5 after 24 h (P < 0.05). GH (500 ng/ml) alone stimulated the IGF-I gene expression markedly (5-to 10-fold increase) after 24 h (P < 0.001). IL-1 beta, and TNF-alpha to a lesser extent, dramatically inhibited the IGF-I mRNA response to GH (IL-1 beta: -82%, P < 0.001 and TNF-alpha: -47%, P < 0.01). The half-maximal inhibition of the IGF-I mRNA response to GH was observed for a concentration of IL-1 beta between 0.1 and 1 ng/ml. Moreover, IL-1 beta abolished the IL-6-induced IGF-I mRNA response. In contrast, IL-6 did not impair the IGF-I mRNA response to GH. To determine the potential role of the GH receptor (GHR) and the GH-binding protein (GHBP) in this GH resistance, we assessed the GHR and GHBP mRNAs response to these cytokines. GH alone did not affect the GHR/GHBP mRNA levels. IL-1 beta markedly decreased the GHR and GHBP mRNA levels (respectively, -68% and -60%, P < 0.05). Neither TNF-alpha nor IL-6 affected the GHR/GHBP gene expression. In conclusion, our results show that IL-1 beta, and TNF-alpha to a lesser extent, blunt the IGF-I mRNA response to GH. The resistance to GH induced by IL-1 beta might be mediated by a decrease of GH receptors, as suggested by the marked reduction of GHR mRNA. These findings suggest that decreased circulating IGF-I, in response to infection and trauma, may be caused by a direct effect of cytokines at the hepatocyte level.
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PMID:Inhibition by interleukin-1 beta and tumor necrosis factor-alpha of the insulin-like growth factor I messenger ribonucleic acid response to growth hormone in rat hepatocyte primary culture. 904 12

The role of p38 mitogen-activated protein kinase (MAPK) in responses of human fibroblasts and vascular endothelial cells to IL-1 was investigated by use of a pyridinyl imidazole compound (SB 203580), which specifically inhibits the enzyme. SB 203580 inhibited (50% inhibitory concentration approximately 0.5 microM) IL-1-induced phosphorylation of heat shock protein 27 (an indicator of p38 MAPK activity) in fibroblasts without affecting the other known IL-1-activated protein kinase pathways (p42/p44 MAPK, p54 MAPK/c-Jun N-terminal kinase and beta-casein kinase). SB 203580 significantly inhibited IL-1-stimulated IL-6, (30 to 50% at 1 microM) but not IL-8 production from human fibroblasts (gingival and dermal) and umbilical vein endothelial cells. IL-1 induction of steady state level of IL-6 mRNA was not significantly inhibited, which is consistent with p38 MAPK regulating IL-6 production at the translational level. SB 203580 strongly inhibited IL-1-stimulated PG production by fibroblasts and human umbilical vein endothelial cells. This was associated with the inhibition of the induction of PGH synthase-2 protein and mRNA. SB 203580 also inhibited the stimulation of collagenase-1 and stromelysin-1 production by IL-1 without affecting synthesis of the tissue inhibitor of metalloproteinases (TIMP)-1. SB 203580 prevented the increase in collagenase-1 and stromelysin-1 mRNA stimulated by IL-1. In a model of cartilage breakdown, short-term IL-1-stimulated proteoglycan resorption and inhibition of proteoglycan synthesis were unaffected by SB 203580, while longer term collagen breakdown was prevented. It is concluded that 1) p38 MAPK plays an important role in the regulation of some, but not all, responses to IL-1, and 2) it is involved in the regulation of mRNA levels of some IL-1-responsive genes.
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PMID:Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase: regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels. 912 Feb 70


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