REGULATION OF CYCLOOXYGENASE-2 EXPRESSION IN BOVINE CHONDROCYTES IN CULTURE BY INTERLEUKIN-1-ALPHA, TUMOR-NECROSIS-FACTOR-ALPHA, GLUCOCORTICOIDS, AND 17-BETA-ESTRADIOL

Objective. To determine the effects of interleukin 1 alpha (IL-1 alpha ), tumor necrosis factor-alpha (TNF-alpha), dexamethasone. and 17 beta -estradiol on the expression of cyclooxygenase-1 (COX-1) and COX-2 in bovine chondrocytes. Methods. Northern blot analysis was used to quant ify COX-1 and COX-2. mRNA expression in primary cultures of bovine cho ndrocytes and prostaglandin production to evaluate COX activity. Resul ts. IL-1 alpha and TNF-alpha increased the expression of COX-2. This e ffect was independent of de novo protein synthesis and dependent on in creased mRNA stability in the case of IL-1 alpha. Dexamethasone inhibi ted the effects of both cytokines. 17 beta-estradiol inhibited COX-2 m RNA expression in basal conditions, but had no effect on COX-2 express ion induced by cytokines. The specific COX-2 inhibitor compound NS 398 prevented the increase in prostaglandin E-2 (PGE(2)) production induc ed by the cytokines. COX-1 levels remained stable with all treatments. Conclusion. Increase in mRNA stability is a mechanism implicated in t he induction of COX-2 by some cytokines. The effects of IL-1 alpha and TNF-alpha on PGE(2) production are mainly due to an increase in COX-2 activity as shown by the effect of compound NS 398, 17 beta-estradiol inhibits COX-2 mRNA expression in basal conditions, suggesting that e strogens could be implicated in the control of cartilage metabolism.