Cyclooxygenase-1 and-2 Expression in Rheumatoid Synovial Tissues Effects of Interleukin-1f, Phorbol Ester, and Corticosteroids

High levels of immunoreactive cyclooxygenase (Cox; prosta-glandin H synthase) are present in synovia from patients with rheumatoid arthritis (RA). We now show that the recently identified inducible isoform ofCox, Cox-2, is expressed in syno-via from patients with RA. To further explore modulation ofthe Cox isoforms in RA synovial tissues, we examined the expres-sion and modulation of Cox-1 and-2 in rheumatoid synovial explant cultures and cultured rheumatoid synovial fibroblast-like cells (synoviocytes). Immunoprecipitation of in vitro la-beled proteins and Western blot analysis demonstrated the pres-ence of both Cox-1 and-2 under basal conditions in freshly explanted rheumatoid synovial tissues. De novo synthesis of Cox-2 polypeptide was enhanced by IL-I1j or PMA, and dra-matically suppressed by dexamethasone (dex). Cox-1 expres-sion, under the same conditions, showed only minor variation. Since mRNA for Cox-2 is highly unstable, we examined the regulation ofCox-2 transcripts in cultured rheumatoid synovio-cytes. Under basal conditions both Cox-1 and-2 mRNAs were present at low levels, but Cox-2 mRNA was markedly in-creased by treatment with I-1jft or PMA. dex markedly sup-pressed the induction of Cox-2 mRNA. In sharp contrast, Cox-1 transcripts were not modulated by IL-1ft or dex. These data suggest that modulation ofCox-2 expression by IL-ift and corti-costeroids may be an important component ofthe inflammatory process in synovial tissues from patients with RA. (J. Clin