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

Abstract.

Objective: Several extracts of Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in patients with rheumatoid arthritis. We investigated the effect of multi-glycosides of TWHF (GTW), a TWHF extract, on interleukin (IL)-1β-stimulated human rheumatoid synovial cells. ¶Materials and Methods: IL-1β-stimulated synovial cells were used to detect the effects of GTW on cyclooxygenase (COX)-1 and COX-2 activities, expression of COX protein and mRNA, and nuclear transcription factors in experiments using respective reporter plasmids. ¶Results: GTW inhibited prostaglandin E₂ production by IL-1β-stimulated synovial cells in a concentration-dependent manner, and also inhibited COX-2 protein and mRNA expression in a similar fashion to dexamethasone. However, GTW did not act as a glucocorticoid agonist. GTW repressed IL-1β-induced nuclear factor-κB activity, but did not have a significant influence on activating protein-1 activity. ¶Conclusion: The anti-rheumatic effect of GTW or TWHF may be partly mediated through the inhibition of prostaglandin E₂ production in human synovial cells due to suppression of COX-2 mRNA, possibly via inhibition of nuclear factor-κB activity.