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)

Human PHA-stimulated mononuclear cells produce a factor which inhibits synovial cell collagen and non-collagen protein synthesis, whereas it enhances hyaluronic acid (HA) production. Indomethacin (10(-4)-10(-6) M), a cyclo-oxygenase inhibitor, suppresses this effect, suggesting that the mechanism is prostaglandin-mediated. The active material, of apparent molecular weight 12 000-20 000, also displays the properties of the mononuclear cell factor (MCF) previously described by others, since its stimulates collagenase and PGE2 release by the cultured synovial cells. Furthermore, it co-purifies with interleukin 1 (IL 1) as shown by lymphocyte-activating factor activity. This strongly suggests that IL 1 could be responsible for some (or all) the effects observed on MCF-exposed synovial cells. From these data, we deduce the possibility that mononuclear cells may participate in limiting synovial collagen deposition in rheumatoid arthritis.
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PMID:Mononuclear cell-mediated modulation of synovial cell metabolism. I. Collagen synthesis. 298 10

In rheumatoid arthritis synovial tissue proliferates and destroys articular cartilage, bone and tendons. Collagenase is a major mediator of the connective tissue degradation. This enzyme is produced in large quantities by rheumatoid tissue and its synthesis can be inhibited by retinoids. However, knowledge of mechanisms controlling retinoid inhibition of collagenase production and of factors possibly controlling synovial cell proliferation is limited. We found that transforming growth factor beta in combination with epidermal growth factor, epidermal growth factor alone and immune interferon increased proliferation of cultured human and rabbit synovial fibroblasts. Only transforming growth factor beta caused a piling up of cells into foci resembling those seen in primary cultures of human rheumatoid tissue. All the factors were antagonized by retinoids but not by glucocorticoids or indomethacin. Adding retinoids or glucocorticoids to collagenase-producing cells decreased hybridizable collagenase mRNA by 50% within 24 h. Oral administration of retinoids to rats with experimental arthritis decreased clinical disease without toxicity, and inhibited collagenase synthesis by synovial cells taken from treated animals. Retinoids are both antiproliferative and anti-invasive, and therefore may be potential therapeutic agents in the treatment of rheumatoid arthritis.
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PMID:Effect of retinoids on rheumatoid arthritis, a proliferative and invasive non-malignant disease. 299 93

The pathogenesis and progression of rheumatoid arthritis involves the production of biologically active lymphokines and monokines. Of these, interleukin 1 (IL-1) has been somewhat of a controversial molecule because it seems to evoke various biological responses in several different tissues. In these studies we demonstrate that three biological properties of human monocyte-derived IL-1 (T-lymphocyte activation and human synovial cell prostaglandin E2 and collagenase production) co-purify. The complementary DNA for the prominent pI 7 form of human IL-1 was expressed, purified, and tested. Any controversy now appears resolved since homogeneous recombinant human IL-1 stimulates prostaglandin E2 and collagenase from human synovial cells as well as activates T cells in vitro.
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PMID:Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells. 300 63

The effects of gold sodium thiomalate (GST) on the production of specific collagenase by thioglycolate-elicited macrophages was investigated. Our studies demonstrated that GST administration can significantly decrease collagenase production in a dose-dependent manner. These effects were observed with levels of GST attainable in serum or synovial tissue during routine chrysotherapy. In addition, GST altered lysozyme secretion by activated macrophages in a pattern distinct from that of collagenase alteration. These effects of enzyme secretion were not secondary effects of GST on viability, general protein secretion, or the specific assay procedures utilized, and were not attributable to the thiomalate moiety. Thus, GST may exert its therapeutic effect in rheumatoid arthritis through interference with the production of degradative proteolytic enzymes, which are important effector molecules mediating tissue destruction.
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PMID:Alterations in macrophage collagenase secretion induced by gold sodium thiomalate. 300 15

Degradation of intact cartilaginous tissue (bovine nasal cartilage) by oxygen-derived free radicals (ODFR) generated enzymatically by xanthine oxidase and hypoxanthine was studied. The degree of tissue destruction was determined by measuring the indentation under a defined compression force as well as by the loss of uronic acid- and hydroxyproline-containing matrix components. Cartilage slices altered by prior elastase treatment were more susceptible to oxygen radical attack than were intact tissue specimens. Degradation of cartilage matrix by ODFR was strongly inhibited by superoxide dismutase or catalase. Coincubation of latent collagenase from polymorphonuclear leukocytes with the ODFR-generating system led to activation of collagenolytic activity, resulting in marked degradation of the bovine cartilage slices. In further studies, activated polymorphonuclear leukocyte-collagenase was shown to degrade intact human articular cartilage to a degree of mechanical insufficiency. Thus, our assay system serves as an in vitro model of tissue damage, which may be relevant to pathophysiologic states such as rheumatoid arthritis.
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PMID:Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes. 300 65

Glutathione peroxidase (Se-GPx) is a selenoenzyme which catalyzes the reduction of hydroperoxides by glutathione (GSH), in most mammalian cells. Several Slow-acting drugs that are used in the treatment of rheumatoid arthritis, including D-Penicillamine, alpha-mercaptopropionylglycine and gold salts, are specific inhibitors of Se-GPx. In situation of oxidant stress, Se-GPx activity is a major source of glutathione disulfide (GSSG), an essential activator of leucocyte collagenase. Hence the possibility that the enzymatic reduction of hydroperoxides produced during chronic inflammation would play an important role in the destruction of joint tissue of arthritic patients. Inhibition of a protective system such as Se-GPx may therefore be involved in the mechanism of action of D-Penicillamine and gold salts, but it could also explain some of their undesirable or toxic effects. Confirmation of this hypothesis would open the way to new pharmacological strategies.
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PMID:[Possible role of glutathione peroxidase in the regulation of collagenase activity]. 301 86

Gold sodium thiomalate, a drug used widely in the therapy of rheumatoid arthritis, was found to be an activator of latent human polymorphonuclear leukocyte collagenase. The activation was demonstrated by two distinct and independent collagenase assays: by recording with a spectrophotometer at 227 nm the enzyme-induced increase in ultraviolet difference absorbance of native type I collagen connected to the cleavage of collagen at 37 degrees C [(1986) Eur. J. Biochem. 156, 1-4] and by SDS-polyacrylamide gel electrophoresis analysis of formation of specific products of collagen resulting from collagenase cleavage at 25 degrees C. Activation of latent collagenase by gold sodium thiomalate appeared to be of the same magnitude as by the known activator phenylmercuric chloride.
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PMID:Gold sodium thiomalate activates latent human leukocyte collagenase. 302 35

To provide tools for understanding collagenase gene expression in rheumatoid arthritis, we have isolated and characterized genomic clones for rabbit synovial cell collagenase. These clones represent 2 types of collagenase gene, at least 1 of which is transcribed in synovial fibroblasts. By examining the rabbit genome in situ, we provide evidence that there are only 2 different synovial cell collagenase genes found in a haploid genome. Amplification of these genes is not a mechanism for collagenase messenger RNA induction by phorbol esters.
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PMID:Characterization of rabbit genes for synovial cell collagenase. 302 58

Collagenase activity of the knee joint menisci of patients suffering from rheumatoid arthritis was approximately 3-fold higher than that found in menisci of control patients. The mean collagenase activity in the macroscopically more diseased parts of the rheumatoid menisci was significantly higher than that in the less damaged areas. The specific degradation products resulting from the cleavage of human meniscoid type II collagen by rheumatoid meniscoid collagenase were demonstrated by SDS-polyacrylamide gel electrophoresis. Addition of N-ethylmaleimide, which activates latent mammalian collagenases, did not further increase collagenase activity in rheumatoid menisci. Thus in rheumatoid meniscus, collagenase may be synthesized and then activated, probably by proteolytic enzymes involved in the inflammatory reaction.
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PMID:Increased collagenase activity in human rheumatoid meniscus. 302 34

The tumorigenic properties of human rheumatoid arthritis synovial cells in culture were investigated. The synovial cells developed good colonies and secreted plasminogen activator (PA) and collagenase in the cell cultures, as do Hela cells. Since PA and progesterone receptor (PgR) are considered to be end products of estradiol action in breast cancer cells, the estrogen receptor (ER) and PgR content in these cells was also assayed. Large amounts of ER and PgR were detected in the synovial cells in culture, even though these cells are not targets for sex steroids. Study of the cytomorphologic changes in the synovial cells in culture revealed many characteristics generally observed in neoplastic cells. Whether any or all of these observations have any implication in prognosis or therapy in this disease remains to be studied.
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PMID:Expression of tumor cell properties in synovial cells in culture. 302 23


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