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)

Urine from monocytic leukemia and other febrile patients contains an inhibitor of interleukin 1 (IL-1), as measured by prostaglandin E2 and collagenase production by human fibroblasts and synovial cells. With the use of recombinant IL-1, the IL-1 inhibitor was partially purified by using ammonium sulfate precipitation, anion-exchange, and gel filtration chromatographies. IL-1 inhibitory activity elutes with an 18,000 to 25,000 apparent molecular size. The same fractions also inhibit IL-1 assayed by the proliferation of murine thymocytes and human fibroblasts. Both forms of human recombinant IL-1, IL-1 alpha and IL-1 beta, which show only 26% homology, but nevertheless bind to the same receptor, are affected by this natural inhibitor to the same extent. In contrast, human recombinant tumor necrosis factor, which shares some of the biologic activities of IL-1, is not inhibited by the urinary IL-1 inhibitor. This study shows that the various biologic activities of both forms of human recombinant IL-1 are inhibited by a partially purified natural urine-derived factor.
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PMID:A urine inhibitor of interleukin 1 activity affects both interleukin 1 alpha and 1 beta but not tumor necrosis factor alpha. 304 Aug 55

Analysis of the conditioned medium from cultured human heart valves showed that these tissues secrete a biologically active factor that induces chondrocytes in cultured cartilage to degrade extracellular matrix proteoglycan. This activity was similar to that described for porcine interleukin-1 (catabolin) and a cytokine secreted by cultured porcine heart valves (cardiac catabolic factor). The biological activity of the material in human valve conditioned medium was unaffected by the presence of low doses of cortisol, but its production by cultured valves was impaired by this steroid or benoxaprofen and abolished by cycloheximide. Addition of the conditioned medium to fibroblast monolayers stimulated the secretion of prostaglandin E and the tissue inhibitor of metalloproteinases (TIMP) but not collagenase. Preincubation of the conditioned medium with antiserum raised to the acidic form of porcine interleukin-1 neutralised the proteoglycan degrading stimulus. The material is biologically similar to other cytokines and antigenically related to porcine interleukin-1.
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PMID:Production of a factor by cultured human heart valves that is immunologically related to interleukin 1. 349 25

Interleukin 1 (IL-1), a monocyte product, exerts a range of biological effects on nonimmune cells such as fibroblasts and chondrocytes including stimulation of synthesis and release of prostaglandin E2 (PGE2) and collagenase. We have previously shown that crude mononuclear cell-conditioned medium, which contains IL-1, also stimulates synthesis of types I and III collagens by human synovial and dermal fibroblasts and chondrocytes when the formation of PGE2, which inhibits collagen synthesis, is blocked by indomethacin. To determine whether IL-1 is responsible for the affects observed using crude monocyte-conditioned medium patterns of collagen synthesis in the three types of human cells in response to recombinant preparations of IL-1 were compared. Preincubation of chondrocytes or synovial fibroblasts with either murine (m)IL-1 alpha or human (h)IL-1 beta alone decreased synthesis of type I collagen and fibronectin. In contrast, when endogenous IL-1-stimulated PGE2 synthesis was blocked by indomethacin, an enhancing effect of IL-1 on synthesis of these matrix proteins was unmasked. The synthesis of type III collagen was enhanced by IL-1 to a greater extent than that of type I collagen in the presence of indomethacin. In human foreskin fibroblasts, which produced low levels of PGE2 even in the presence of IL-1, synthesis of types I and III collagens was increased by IL-1 either in the absence or presence of indomethacin. These cells were more responsive to the hIL-1 beta preparation than to the mIL-1 alpha (half-maximal stimulation of PGE2 production was observed at approximately 2.5-5 pM hIL-1 beta and at approximately 2.5 nM mIL-1 alpha). Levels of alpha 1 (I), alpha 2(I), and alpha 1(III) procollagen mRNAs measured by cytoplasmic dot hybridization paralleled the levels of collagens synthesized under the various experimental conditions. IL-1, therefore, is one product of monocytes capable of modulating collagen synthesis by these human mesenchymal cells probably by altering collagen gene expression. These studies suggest that both positive (IL-1) and negative (PGE2) signals may control collagen synthesis at the transcriptional level resulting in modulation of matrix turnover in cartilage, synovium, and skin.
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PMID:Modulation by recombinant interleukin 1 of synthesis of types I and III collagens and associated procollagen mRNA levels in cultured human cells. 350 Jan 70

Homogeneous catabolin from pig leucocytes induced proteoglycan breakdown, but not collagen breakdown, in explants of articular cartilage. It augmented lectin-induced proliferation of mouse thymocytes, stimulated production of prostaglandin E2 and collagenase by fibroblasts and chondrocytes, and increased Ca2+ release from mouse calvarial explants, all at concentrations down to 50 pM. In view of these effects it was concluded that pig catabolin is a form of interleukin 1.
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PMID:Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandin and collagenase, and thymocyte proliferation is augmented in response to one protein. 609 18

Resorption of cartilage matrix is usually considered to be due to extrinsic proteases, generally thought to be the neutral metalloproteases, including collagenase. Such enzymes can be secreted from synovial tissue and in acute forms of arthritis they are believed to be the main agents of pannus erosion. However, such enzyme secretion has not been clearly demonstrated to be the causative agent in either rheumatoid arthritis or in osteoarthritis. For example, no specific inhibitors of these proteinases have yet been proved effective in vivo. Recent experiments at the Strangeways Research Laboratory have demonstrated that viable chondrocytes of animal and human articular cartilage are capable of resorbing their surrounding matrix without the aid of extrinsic enzymes. We now know that such resorption can be stimulated by the action of a low molecular weight peptide released from living synovial and other connective tissues. These messengers (catabolins) are capable of stimulating chondrocytes to degrade totally both proteoglycan and collagen. The purification, properties, regulation and action of catabolism are under investigation to determine the role for catabolin in arthritis.
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PMID:Catabolin--a cartilage catabolic factor from synovium. 701 63

Interleukin-1 beta (IL-1 beta) may be related to the pathological processes associated with periodontitis, primarily due to its ability to induce collagenase, increase neutrophil chemotaxis, and stimulate bone resorption. This study was designed to histologically quantitate IL-1 beta positive cells from various histologic fields in untreated gingivitis/early periodontitis (G/EP) versus moderate/severe periodontitis (M/SP) gingival tissues, and associate these with collagen loss. Two gingival biopsies from 8 patients were collected, one from a G/EP site and one from a M/SP site. Mouse monoclonal antibodies in combination with an avidin-biotin-peroxidase system were used to stain for IL-1 beta, while the van Gieson method was used to stain for collagen in serial sections. Collagen loss in G/EP (35%) and M/SP (52%) fields was consistent with gingivitis and periodontitis, respectively. IL-1 beta positive cells in combined coronal/sulcular (Co/Su) and apical/sulcular (Ap/Su) fields (nearest the bacterial insult) were significantly more numerous compared to combined coronal/middle (Co/Mi) and apical/middle (Ap/Mi) fields (p < 0.05). While numbers and percentages of IL-1 beta positive cells were generally higher in M/SP biopsies, differences were not significant. Further, there was no correlation between the number of IL-1 beta positive cells and percent collagen loss. However, a significant correlation between IL-1 beta positive cells and corresponding gingival crevicular fluid IL-1 beta concentrations was noted (r = 0.65, p = 0.01). Through the use of immunohistochemistry, this study demonstrated that the presence of IL-1 beta + cells does not appear to have a direct association with collagen loss.
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PMID:Histological evaluation of interleukin-1 beta and collagen in gingival tissue from untreated adult periodontitis. 750 86

To examine potential mechanisms by which hematopoiesis may be regulated by endothelial cells within the bone marrow (BM) microenvironment, we have devised a technique for the in vitro study of the interaction of human BM microvascular endothelial cells (BMEC) with hematopoietic cells. Microvessels isolated by collagenase digestion of spicules obtained from filtered BM aspirate were plated on gelatin-coated plastic dishes, and colonies of endothelial cells grown from microvessel explants were further purified by Ulex europaeus lectin affinity separation. BMEC monolayers isolated by this technique grew in typical cobblestone fashion, stained positively with antibody to factor VIII/von Willebrand factor, and incorporated acetylated LDL. Immunohistochemical studies showed that BM microvessels and BMEC monolayers express CD34, PECAM, and thrombospondin. Incubation of resting BMEC with BM mononuclear hematopoietic cells resulted in the selective adhesion of relatively large numbers of CD34+ progenitor cells and megakaryocytes. The binding of purified BM-derived CD34+ progenitor cells to BMEC was dependent on divalent cations and was partially blocked by antibodies to CD34. IL-1 beta treatment of BMEC monolayers resulted in an increase of CD34+ progenitor cell adhesion by mechanisms independent of CD34 or divalent cations. BMEC exhibit specific affinity for CD34+ progenitor cells and megakaryocytes, suggesting that the BM microvasculature may play a role in regulating the trafficking, proliferation, and differentiation of lineage specific hematopoietic elements, and possibly of pluripotent stem cells within the CD34+ population.
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PMID:Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion. 751 3

Nitric oxide (NO.) is a multifunctional messenger molecule generated by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO. in the modulation of two metal-dependent proteolytic enzymes (collagenase and stromelysin) which are activated during inflammatory and infective arthritis. The inflammatory mediators interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and the bacterial cell wall fragment endotoxin, induced both nitric oxide synthase activity and stromelysin and collagenase activity in whole cell preparations and in conditioned media from explants of bovine and human cartilage. Both NO2- (the stable end-product of NO.) and metalloprotease activity were inhibited by competitive inhibitors of nitric oxide synthase. The NO. donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP) also induced metalloprotease activity in a dose-dependent fashion. These data provide evidence that NO. plays a regulatory role in the activation of metal-dependent proteases in articular chondrocytes and cartilage.
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PMID:Nitric oxide activates metalloprotease enzymes in articular cartilage. 752 96

The fibroblast is a prominent cellular component of the periodontal ligament. It is believed to play an important role in collagen metabolism in health and disease. The turnover of collagen in the periodontal ligament is believed to be controlled by the balance between collagen synthesis and degradation. The family of matrix metalloproteinases and their inhibitors is one of the mechanisms which regulates this balance. The factors that regulate the synthesis of collagenase and its inhibitor, TIMP-1, by the periodontal ligament cell are poorly understood. The present study was undertaken to assess the effect of interleukin-1 beta (IL-1 beta), platelet-derived growth factor (PDGF), and transforming growth factor-beta 1 (TGF-beta) on the expression of collagenase (MMP-1) and TIMP-1 mRNA in periodontal derived fibroblasts using reverse transcription polymerase chain reaction (RT-PCR). Early passage periodontal ligament derived fibroblasts were treated with IL-1 beta (10 and 100 pg/ml), two isoforms of PDGF, -AA and -BB (4 and 20 ng/ml) and TGF-beta (1 and 10 ng/ml). Treatment with growth factors from 2 to 24 hours revealed that the largest effects on MMP-1 mRNA occurred after 24 hours. IL-1 beta induced a 5 to 9 fold increase in MMP-1 mRNA. The two isoforms of PDGF had less of an effect (3 to 5 fold) on MMP-1 mRNA whereas TGF-beta induced a 25 to 50% decrease in the expression of this message. None of the growth factors had an effect on TIMP-1 mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth factor effects on the expression of collagenase and TIMP-1 in periodontal ligament cells. 756 46

The expression of the matrix-degrading enzymes collagenase and stromelysin is modulated by a variety of biologic and pharmacologic agents. IFN-gamma has potent effects on metalloproteinase production and therefore may play an important role in preventing excessive connective tissue degradation during inflammation and repair. We investigated the mechanisms of collagenase and stromelysin regulation by IFN-gamma in human dermal fibroblasts. IFN-gamma (300 U/ml) prevented the stimulation of metalloproteinase gene expression by IL-1 beta. In addition, incubation of fibroblasts with IFN-gamma resulted in a marked increase in cellular indoleamine 2,3-dioxygenase (IDO) mRNA, a > 90% depletion of tryptophan, and a corresponding > 30-fold increase in the tryptophan metabolite kynurenine in the culture media. Reducing the concentration of tryptophan from 25 microM to 0 markedly diminished the ability of fibroblasts to increase collagenase and stromelysin mRNA and collagenase production in response to IL-1 beta. Addition of exogenous tryptophan (25-50 micrograms/ml) to cultures that had been tryptophan depleted by pretreatment with IFN-gamma for 48 h restored the fibroblast response to IL-1 beta or PMA, but had no effect on IFN-gamma-induced HLA-DR alpha chain mRNA expression. These results indicate that inhibition of collagenase and stromelysin gene expression by IFN-gamma in fibroblasts is associated with activation of IDO and enhanced cellular tryptophan metabolism. Tryptophan degradation and ensuing tryptophan depletion may account, at least in part, for the inhibitory effect of IFN-gamma on metalloproteinase production in dermal fibroblasts.
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PMID:Inhibition of collagenase and stromelysin gene expression by interferon-gamma in human dermal fibroblasts is mediated in part via induction of tryptophan degradation. 761 20


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