PMID- 15184078 OWN - NLM STAT- MEDLINE DCOM- 20040730 LR - 20121115 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 319 IP - 3 DP - 2004 Jul 2 TI - Triptolide (PG-490) induces apoptosis of dendritic cells through sequential p38 MAP kinase phosphorylation and caspase 3 activation. PG - 980-6 AB - Dendritic cells (DCs) are the most potent antigen-presenting cells that play crucial roles in the regulation of immune response. Triptolide, an active component purified from the medicinal plant Tripterygium wilfordii Hook F., has been demonstrated to act as a potent immunosuppressive drug capable of inhibiting T cell activation and proliferation. However, little is known about the effects of triptolide on DCs. The present study shows that triptolide does not affect phenotypic differentiation and LPS-induced maturation of murine DCs. But triptolide can dramatically reduce cell recovery by inducing apoptosis of DCs at concentration as low as 10ng/ml, as demonstrated by phosphatidylserine exposure, mitochondria potential decrease, and nuclear DNA condensation. Triptolide induces activation of p38 in DCs, which precedes the activation of caspase 3. SB203580, a specific kinase inhibitor for p38, can block the activation of caspase 3 and inhibit the resultant apoptosis of DCs. Our results suggest that the anti-inflammatory and immunosuppressive activities of triptolide may be due, in part, to its apoptosis-inducing effects on DCs. FAU - Liu, Qiuyan AU - Liu Q AD - Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China. FAU - Chen, Taoyong AU - Chen T FAU - Chen, Huabiao AU - Chen H FAU - Zhang, Minghui AU - Zhang M FAU - Li, Nan AU - Li N FAU - Lu, Zhanjun AU - Lu Z FAU - Ma, Pengcheng AU - Ma P FAU - Cao, Xuetao AU - Cao X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Diterpenes) RN - 0 (Epoxy Compounds) RN - 0 (Immunosuppressive Agents) RN - 0 (Phenanthrenes) RN - 19ALD1S53J (triptolide) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) SB - IM MH - Animals MH - Apoptosis/*physiology MH - Caspase 3 MH - Caspases/*metabolism MH - Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/cytology/*drug effects/metabolism MH - Diterpenes/*pharmacology MH - Enzyme Activation MH - Epoxy Compounds MH - Immunosuppressive Agents/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinases/*metabolism MH - Phenanthrenes/*pharmacology MH - Phenotype MH - Phosphorylation MH - p38 Mitogen-Activated Protein Kinases EDAT- 2004/06/09 05:00 MHDA- 2004/07/31 05:00 CRDT- 2004/06/09 05:00 PHST- 2004/04/03 00:00 [received] PHST- 2004/06/09 05:00 [pubmed] PHST- 2004/07/31 05:00 [medline] PHST- 2004/06/09 05:00 [entrez] AID - S0006291X04009404 [pii] AID - 10.1016/j.bbrc.2004.04.201 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2004 Jul 2;319(3):980-6. doi: 10.1016/j.bbrc.2004.04.201.