RELATIONSHIPS, AMONG STEROIDS, OF ANTIINFLAMMATORY PROPERTIES AND INHIBITION OF PROSTAGLANDIN PRODUCTION AND ARACHIDONIC-ACID RELEASE BY TRANSFORMED MOUSE FIBROBLASTS

Abstract

Anti-inflammatory steroids [dexamethasone, betamethasone, 9.alpha.-fludrocortisol, triamcinolone, prednisolone, hydrocortisone, cortisone, corticosterone and arachidonic acid] inhibit serum-stimulated prostaglandin synthesis and release of 3H-arachidonic acid by methylcholanthrene-transformed mouse fibroblast, MC5-5. The half-maximal concentration for inhibition of both effects parallels the relative anti-inflammatory potencies of these steroids. The fatty acid cyclooxygenase activities of microsomal fractions isolated from cells that were pretreated with dexamethasone were similar to activities of microsomal fractions isolated from untreated cells. Intracellular and extracellular levels of prostaglandins in dexamethasone inhibited cells were decreased. Anti-inflammatory steroids seem to be blocking deacylation of the phospholipids or transport of the arachidonic acid, after deacylation, to the cyclooxygenase.