COX-2 in synovial tissues

Abstract

Prostaglandins (PGs) are important mediators of acute and chronic inflammation. The production of PGs in synovial tissues is catalyzed by an enzyme cascade that includes phospholipase A2s (PLA2s), cyclooxygenases (COXs), and terminal PG synthases. There are two isoforms of COX expressed in synovial tissues. COX-1 is constitutively expressed in synovia, particularly in synovial lining cells. COX-2, on the other hand, is localized most strikingly to the vascular endothelial cells, mononuclear inflammatory cells, and subsynovial fibroblasts. There are no significant differences in immunostaining of COX-1 in vivo in inflammatory compared with non- inflammatory arthritis. COX-2 expression is increased in inflammatory arthritis. In-vitro, COX-2 expression in synovial cells is dramatically increased by proinflammatory cytokines, phorbol ester, and stimulation of certain cell surface receptors. A number of different transcription factors are likely to be involved in the up-regulation of COX-2 in synovial tissues. Expression of COX-2 is inhibited by glucocorticoids in synovial cells as in other cell types. Taken together, these data suggest that COX-2 is likely to be responsible for increased local PG production during inflammation of synovial tissues.