The aim of this study was to confirm the involvement of cyclooxygenase (COX)-1 in rheumatoid arthritis (RA).
Synovial cells isolated from arthritic patients were cultured primarily and consecutively for 8 passages.
The cultured synovial cells were incubated with 10 ng/ml of interleukin-1alpha (IL-1alpha) for 6 h.
The effects of either COX-1 or COX-2 selective inhibitor on prostaglandin E2 (PGE2) production was estimated by enzyme-linked immunosorbent assay (ELISA) and the expression of COX-1 and COX-2 were determined by Western blotting and immunocytochemistry.
IL-1alpha-induced PGE2 production in synovial cells isolated from RA in primary culture was inhibited by mofezolac, a selective inhibitor of COX-1, as well as NS-398, a specific inhibitor of COX-2. The similar inhibitory patterns were obtained in the RA-derived synovial cells within 3 passages. However, COX activity in the RA-derived synovial cells after 5 passages was inhibited by NS-398, but not by mofezolac. In contrast, COX activity in primary and consecutively cultured synovial cells isolated from osteoarthritis (OA) or normal arthritis was inhibited by NS-398, but not by mofezolac. Western blot and immunocytochemical analyses of COX-1 and COX-2 in the synovial cells isolated from RA patients within 3 passages showed an induction in both COX-1 and COX-2 expression by IL-1alpha. The induction of both COX-1 and COX-2 was inhibited by dexamethasone.
These experiments demonstrate COX-1 induction in synovial cells isolated from RA patients, suggesting that COX-1 is involved in the progression of RA.