Effect of ICI 55897 (Clozic), indomethacin and dexamethasone on collagenase and prostaglandin production by cultured rheumatoid synovial tissue (Abstract)
Expiants of rheumatoid synovial tissue produce significant quantities of neutral collagenase and prostaglandins when cultured for 5–6 days at 37°C in serum-free Dulbecco’s modified Eagle’s medium (Dayer et al. (1976). Proc. Natl. Acad. Sci. (USA), 73, 945). Cultures which were supplemented with ICI55897 over the concentration range 20–400 μg/ml (all culture flasks contained 10 mg/ml human serum albumin) showed no significant change in the production of either total collagenase or prostaglandins. Total collagenase was measured using the 14C-labelled collagen fibril assay following trypsin activation of culture medium, and the prostaglandins PGE2 and PGF2α were measured by radio-immunassay. No change was detected in glucose depletion or lactate dehydrogenase activity of the culture medium, suggesting that viability over 5 days of culture was similar to that of the controls. Most experiments were carried out using a concentration of 150 μg/ml of ICI 55897 and no change was detected for levels of the prostaglandins PGE2 and PGF2α although a slight reduction in collagenase was occasionally observed. In contrast, indomethacin (5 μg/ml) inhibited all prostaglandin production, but had a variable effect on collagenase production which occasionally was slightly higher than control values. Dexamethasone (10-7mol/l) was shown to inhibit both collagenase and prostaglandin production.