Yang Y, Liu Z, Tolosa E, Yang J, Li L
Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Immunopharmacology. 1998 Aug;40(2):139-49. doi: 10.1016/s0162-3109(98)00036-8.
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 investigate its effect on activation of T lymphocytes, we found triptolide induces apoptotic death of T cell hybridomas and peripheral T cells but not that of thymocytes. The triptolide-induced apoptosis is accompanied by increase of DEVD-cleavable caspases activity and degradation of caspase substrate poly (ADP-ribose) polymerase (PARP). A specific inhibitor of caspases, zVAD-FMK, prevents triptolide-induced PARP degradation and DNA fragmentation but not growth arrest. Furthermore, enforced expression of Bcl-2 inhibited triptolide-induced degradation of PARP 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 immunosuppressive activity of TWHf extract.
