Cyclooxygenase (COX), or prostaglandin (PG) H synthase, is the first exzyme of the pathway in which arachidonic acid is oxidized to PGs. We previously reported that high levels of immunoreactive COX were present in synovia from patients with rheumatoid arthritis (RA), but not in synovia from patients with osteoarthritis (OA) or normal subjects. An inducible isoform of COX, COX2, has recently been identified.
So we examined the expression and modulation of both COX1 and COX2 in rheumatoid synovial tissues and cultured synoviocytes. COX1 and 2 mRNA were present in synovia from RA patients by RT-PCR method. Immunostaining with anti-COX1 and 2 antibodies showed that high levels of COX1 and 2 polypeptides were expressed in rheumatoid synovial tissues (synovial lining cell layer, inflammatory mononuclear cells, fibroblast-like cells, vascular endothelial cells) . Significantly less staining of COX1 and 2 was noted in OA synovia. In cultured rheumatoid synoviocytes under basal condition, both COX1 and 2 mRNA were present at low levels. COX2 mRNA was markedly increased by treatment with IL-1β or PMA. Dexamethason (Dex) suppressed the induction of COX2 mRNA. In sharp contrast, COX1 mRNA was not induced with IL-1β, and Dex did not have suppressive effects.
We suggest that the regulation of COX2 by IL-1β and corticosteroids may be important mechanisms to regulate inflammation in synovial tissues from RA patients.
