Collagenase production by human mononuclear cells in culture: inhibition by gold containing compounds and other antirheumatic agents.
Human peripheral blood mononuclear cells in adherent cultures have been shown to synthesise and secrete collagenase. In the present study we have examined the modulation of collagenase production in these cultures by several antirheumatic agents. Incubation of monocytes in serum free medium with sodium aurothiomalate in concentrations varying from 7.7 X 10(-7) to 7.7 X 10(-3) mol/l resulted in marked dose dependent inhibition of the collagenase production. This inhibition was apparently selective in that total protein synthesis or the viability of the cells were not affected. Similar inhibition of the collagenase production was also noted with auranofin, aurothioglucose, and chloroauric acid. The inhibition with auranofin was achieved with a concentration as low as 7.4 X 10(-8) mol/l. To examine the mechanisms of the inhibition of the collagenase activity induced by sodium aurothiomalate the production of prostaglandin E2 was also measured in the same cell cultures. Sodium aurothiomalate in concentrations greater than 7.7 X 10(-4) mol/l significantly inhibited the prostaglandin E2 production; the prostaglandin E2 production was not inhibited, however, in 7.7 X 10(-5) mol/l concentration, while the collagenase production was reduced by 51.0%. Also, exogenous prostaglandin E2 added to the cultures only slightly reversed the inhibition of the collagenase production by sodium aurothiomalate. Thus the inhibition of collagenase production by sodium aurothiomalate in human adherent mononuclear cell cultures appears to be independent of the inhibition of prostaglandin E2 production. The inhibition of collagenase produced by monocyte-macrophages, as shown here in vitro, may contribute to the clinical efficacy of the compounds tested in the treatment of rheumatoid arthritis.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology; D002478:Cells, Cultured; D002498:Centrifugation; D006046:Gold / Q000494:pharmacology*; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006432:Hemochromatosis / Q000201:enzymology; D006801:Humans; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009000:Monocytes / Q000201:enzymology* / Q000378:metabolism; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D014176:Protein Biosynthesis
D000893:Anti-Inflammatory Agents; D011458:Prostaglandins E; D006052:Gold Sodium Thiomalate; D001310:Auranofin; D006046:Gold; D003012:Microbial Collagenase