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 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.
Yang
Y
Y
Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. yiliyang@box-y.nih.gov
Liu
Z
Z
Tolosa
E
E
Yang
J
J
Li
L
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004852:Epoxy Compounds; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; C001899:triptolide; D020169:Caspases