The molecular mechanism of inhibition of interleukin-1 beta-induced cyclooxygenase-2 expression in human synovial cells by Tripterygium wilfordii Hook F extract

Objective: Several extracts of Tripterygium wilfordii Hook F (TWHF) have be en reported to be effective in patients with rheumatoid arthritis. We inves tigated the effect of multi-glycosides of TWHF (GTW), a TWHF extract, on in terleukin (TL)-1 beta-stimulated human rheumatoid synovial cells. Materials and Methods. IL-1 beta-stimulated synovial cells were used to detect the e ffects of GTW on cyclooxygenase (COX)-1 and COX-2 activities, expression of COX protein and mRNA, and nuclear transcription factors in experiments usi ng respective reporter plasmids. Results: GTW inhibited prostaglandin E-2 production by IL-1 beta-stimulated synovial cells in a concentration-dependent manner, and also inhibited COX -2 protein and mRNA expression in a similar fashion to dexamethasone. Howev er, GTW did not act as a glucocorticoid agonist. GTW repressed IL-1 beta-in duced nuclear factor-kappa B activity, but did not have a significant influ ence on activating protein-1 activity. Conclusion: The anti-rheumatic effect of GTW or TWHF may be partly mediated through the inhibition of prostaglandin E-2 production in human synovial c ells due to suppression of COX-2 mRNA, possibly via inhibition of nuclear f actor-kappa B activity.