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)

Recent work from this laboratory has shown that macrophages in culture synthesize and secrete a soluble factor(s) that induces the synthesis of collagenase in primary cultures of rabbit chondrocytes (Arth. Rheum. 23, 448, 1980). The current studies were undertaken to determine the role of arachidonate metabolism in this process. Incubation of chondrocytes with MCM (Macrophage Conditioned Medium) and low doses of indomethacin (1-10 microM) had no effect on collagenase synthesis. The lipoxygenase inhibitor NDGA, indomethacin at high doses (50 microM), diethylcarbamazine and the phospholipase inhibitor dibromoacetophenone, inhibited the MCM dependent synthesis of collagenase in chondrocytes. These inhibitors did not affect collagenase activity nor did they interfere with the activation of latent collagenase. Our data indicate that although cyclooxygenase plays no role in the MCM dependent induction of collagenase in chondrocytes, lipoxygenase activity may be essential.
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PMID:Studies on the effects of cyclo-oxygenase and lipoxygenase inhibitors on the macrophage stimulated synthesis of collagenase by rabbit chondrocytes. 300 57

Previous studies have demonstrated that exposure of guinea pig macrophages to a primary signal, such as lipopolysaccharide (LPS), stimulates the synthesis of prostaglandin E2 (PGE2) which, in turn, elevates cAMP levels resulting in the production of the enzyme, collagenase. The potential of regulating the biochemical events in this activation sequence was examined with the anti-inflammatory agents dexamethasone and colchicine, which suppress the destructive sequelae in chronic inflammatory lesions associated with the degradation of connective tissue. The addition of dexamethasone with LPS to macrophage cultures resulted in a dose-dependent inhibition of PGE2 and collagenase production, which was reversed by the exogenous addition of phospholipase A2. Collagenase production was also restored in dexamethasone-treated cultures by the addition of products normally produced as a result of phospholipase action, such as arachidonic acid, PGE2 or dibutyryl-cAMP. Since the effect of dexamethasone was thus linked to phospholipase A2 inhibition, mepacrine, a phospholipase inhibitor, was also tested. Mepacrine, like dexamethasone, caused a dose-dependent inhibition of PGE2 and collagenase. In addition to corticosteroid inhibition, colchicine was also found to block collagenase production. However, this anti-inflammatory agent had no effect on PGE2 synthesis. Colchicine was effective only when added at the onset of culture and not 24 h later, implicating a role for microtubules in the transmission of the activation signal rather than enzyme secretion. The failure of lumicolchicine to inhibit collagenase activity provided additional evidence that microtubules are involved in the activation of macrophages. These findings demonstrate that dexamethasone and colchicine act at specific steps in the activation sequence of guinea pig macrophages to regulate collagenase production.
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PMID:Regulation of guinea pig macrophage collagenase production by dexamethasone and colchicine. 632 92