TRIPTOLIDE INDUCES APOPTOTIC DEATH OF T-LYMPHOCYTE

Extract of Tripterygium wilfordii Hook. f (TWHf) has immunosuppressive activity and has been used as anti-inflammatory agent in traditional Chinese medicine for centuries. Recent studies have demonstrated that triptolide is the major active component in the extract that inhibits antigen or mitogen-induced T cell proliferation. In attempting to inve stigate its effect on activation of T lymphocytes, we found triptolide induces apoptotic death of T cell hybridomas and peripheral T cells b ut not that of thymocytes. The triptolide-induced apoptosis is accompa nied by increase of DEVD-cleavable caspases activity and degradation o f caspase substrate poly (ADP-ribose) polymerase (PARP). A specific in hibitor of caspases, zVAD-FMK, prevents triptolide-induced PARP degrad ation and DNA fragmentation but not growth arrest. Furthermore, enforc ed expression of Bcl-2 inhibited triptolide-induced degradation of PAR P and apoptosis. These results indicate that triptolide induces T cell apoptosis through activating caspases, and suggest the growth arrest and apoptotic effect of triptolide may contribute to the immunosuppres sive activity of TWHf extract. (C) 1998 Elsevier Science B.V. All righ ts reserved.