EFFECTS OF TRIPTERYGIUM-WILFORDII HOOK F-EXTRACT ON INDUCTION OF CYCLOOXYGENASE-2 ACTIVITY AND PROSTAGLANDIN E-2 PRODUCTION

Objective. Extracts of the Chinese herbal remedy Tripterygium wilfordi i Hook F (TWHF) have been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, but the mechanism of this therapeutic effect has not been completely delin eated. The present study was designed to assess the effects of TWHF on the in vitro synthesis of prostaglandin E-2 (PGE(2)) and on the expre ssion of the cyclooxygenase isoforms, COX-1 and COX-2, in various huma n cell types. Methods. Monocytes from human peripheral blood (HM), fib roblasts from rheumatoid arthritis synovial tissue (RASF), human neona tal foreskin fibroblasts (HFF), and the histocytic cell line U937 were cultured for designated time periods with or without lipopolysacchari de (LPS), and in the presence or absence of varying concentrations of the following inhibitors: the methanol/chloroform (T2) extract of TWHF , the ethyl acetate (EA) extract of TWHF, a purified diterpenoid compo nent of TWHF (triptolide), dexamethasone, and indomethacin. Culture su pernatants were harvested for PGE(2) content assays. Total RNA was ext racted from the cells and analyzed for COX-1 and COX-2 messenger RNA ( mRNA) expression using reverse transcriptase-polymerase chain reaction or Northern blotting. Results. Both the T2 and EA extracts inhibited PGE(2) synthesis in the LPS-stimulated HM, RASF, and HFF cells, which was reflected by a marked suppression in the levels of mRNA for COX-2. In contrast, neither extract inhibited PGE(2) production in U937 cell s that did not express COX-2. Triptolide also inhibited LPS-stimulated induction of COX-2 mRNA and synthesis of PGE(2), at the same inhibito ry concentration as seen with the EA extract. The effects of T2, EA, a nd triptolide paralleled the inhibitory action of dexamethasone. Concl usion. The data indicate that both the T2 and EA extracts of TWHF, as well as the triptolide component, inhibit PGE(2) production in a varie ty of human cells by blocking the up-regulation of COX-2.