COX-2 Expression and Regulation in Synovial Tissues

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 12 (V 43). 1998;

Abstract: Dept. of Medicine University of Michigan Ann Arbor MI Prostaglandins (PGs) are important mediators of inflammation and tissue destruction in patients with rheumatoid arthritis (RA). PG production is regulated by an enzymatic cascade with cyclooxygenase (COX PGH synthase) as the central enzyme in the conversion of arachidonic acid to PGs. It has been proposed that COX-1 and COX-2 subserve different physiologic functions largely because of the striking differences in their tissue expression and regulation. COX-1 is constitutively expressed in almost all tissues and appears to be responsible for the production of PGs important for homeostatic functions. In contrast expression of COX-2 under basal conditions is quite restricted. COX-2 produces PGs important for some physiologic functions such as in reproduction. COX-2 is also the isoform responsible for increased PG production during inflammation and dysregulated proliferation. COX-2 expression is rapidly inducible and tightly regulated in inflammatory joint diseases. In animal models of inflammatory arthritis COX-2 increases in parallel with PG production and clinical inflammation and inhibition of COX-2 is equally effective to non-selective COX inhibition in decreasing inflammation. COX-2 is present in vivo in rheumatoid synovia to a greater extent that patients with OA. In RA synovial tissues in vitro COX-2 expression is increased by IL-1 § and TNF-a and decreased by glucocorticoids. Upregulated COX-2 mRNA expression by proinflammatory cytokines involves NF-kB however other transcription factors are likely to be important in the regulation of COX-2 in synovial cells. Basal and stimulated PG production is inhibited equally well by non-selective COX inhibitors and selective COX-2 inhibitors. Although some questions remain unanswered these data suggest that inhibition of COX-2 will provide effective anti-inflammatory therapy for patients with RA and other forms of inflammatory arthritis. ... le

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