Triptolide induces apoptotic death of T lymphocyte
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Triptolide induces apoptotic death of T lymphocyte. / Yang, Y; Liu, Z; Tolosa, E; Yang, J; Li, L.
In: IMMUNOPHARMACOLOGY, Vol. 40, No. 2, 01.08.1998, p. 139-49.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Triptolide induces apoptotic death of T lymphocyte
AU - Yang, Y
AU - Liu, Z
AU - Tolosa, E
AU - Yang, J
AU - Li, L
PY - 1998/8/1
Y1 - 1998/8/1
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis
KW - Caspases
KW - Cell Division
KW - Diterpenes
KW - Enzyme Activation
KW - Epoxy Compounds
KW - Humans
KW - Immunosuppressive Agents
KW - Interleukin-2
KW - Lymphocyte Activation
KW - Mice
KW - Phenanthrenes
KW - Proto-Oncogene Proteins c-bcl-2
KW - Proto-Oncogene Proteins c-fos
KW - T-Lymphocytes
M3 - SCORING: Journal article
C2 - 9826028
VL - 40
SP - 139
EP - 149
JO - IMMUNOPHARMACOLOGY
JF - IMMUNOPHARMACOLOGY
SN - 0162-3109
IS - 2
ER -