CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 EXPRESSION IN RHEUMATOID SYNOVIAL TISSUES - EFFECTS OF INTERLEUKIN-1-BETA, PHORBOL ESTER, AND CORTICOSTEROIDS

High levels of immunoreactive cyclooxygenase (Cox; prostaglandin H syn thase) are present in synovia from patients with rheumatoid arthritis (RA). We now show that the recently identified inducible isoform of Co x, Cox-2, is expressed in synovia from patients with RA. To further ex plore modulation of the Cox isoforms in RA synovial tissues, we examin ed the expression and modulation of Cox-1 and -2 in rheumatoid synovia l explant cultures and cultured rheumatoid synovial fibroblastlike cel ls (synoviocytes). Immunoprecipitation of in vitro labeled proteins an d Western blot analysis demonstrated the presence of both Cox-1 and -2 under basal conditions in freshly explanted rheumatoid synovial tissu es. De novo synthesis of Cox-2 polypeptide was enhanced by IL-1 beta o r PMA, and dramatically suppressed by dexamethasone (dex). Cox-1 expre ssion, under the same conditions, showed only minor variation. Since m RNA for Cox-2 is highly unstable, we examined the regulation of Cox-2 transcripts in cultured rheumatoid synoviocytes. Under basal condition s both Cox-1 and -2 mRNAs were present at low levels, but Cox-2 mRNA w as markedly increased by treatment with IL-1 beta or PMA. dex markedly suppressed the induction of Cox-2 mRNA. In sharp contrast, Cox-1 tran scripts were not modulated by IL-1 beta or dex. These data suggest tha t modulation of Cox-2 expression by IL-1 beta and corticosteroids may be an important component of the inflammatory process in synovial tiss ues from patients with RA.