[Effects of triptolide on the production of interferon-gamma in human peripheral blood mononuclear cell and phosphorylation of signal transducer and activator of transcription-1 and production of interleukin-8].
OBJECTIVE
To investigate the effects of triptolide on the production of interferon-gamma (IFN-gamma) in human peripheral blood mononuclear cell (PBMC) and interleukin-8 (IL-8) in HaCaT keratinocytes and phosphorylation of signal transducer and activator of transcription-1 (STAT1) of IFN-gamma signal transduction pathways in HaCaT cells.


METHODS
Human PBMC was induced by phytohaemagglutinin (PHA-L) and HaCaT cells were stimulated by recombinant human IFN-gamma (rhIFN-gamma). The productions of IFN-gamma and IL-8 in cells were detected by ELISA. The expression of STAT1 and its phosphorylation were analyzed by Western blot.


RESULTS
Triptolide inhibited the production of IFN-gamma in human PBMC induced by PHA-L in a dose-dependent manner (P < 0.05, P < 0.01, P < 0.001) and the 50% inhibitory concentration (IC50) value was 5.96 x 10(-11) mol/L. IL-8 production in HaCaT cells induced by rhIFN-gamma in vitro was also inhibited by triptolide (P < 0.001) and the IC50 value was about 1.15 x 10(-13) mol/L. The expressions of phosphorylated STAT1 in HaCaT cells stimulated by rhIFN-gamma was inhibited by triptolide (P < 0.01) and the IC50 value was about 9.45 x 10(-11) mol/L.


CONCLUSIONS
Triptolide can inhibit the production of IFN-gamma in human PBMC and downregulate IL-8 level in HaCaT keratinocytes induced by rhIFN-gamma. Triptolide can inhibit the phosphorylations of STAT1 of IFN-gamma signal pathway in HaCaT keratinocytes stimulated by IFN-gamma.
Li
Xin-Yu
XY
Department of Pharmacology, Institute of Dermatology, CAMS and PUMC, Nanjing 210042, China. xinyusli609@yahoo.com.cn
Qian
Zhi-Yu
ZY
Gao
Ji-Wei
JW
Zheng
Jia-Run
JR
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D016209:Interleukin-8; D010616:Phenanthrenes; D050794:STAT1 Transcription Factor; C001899:triptolide; D007371:Interferon-gamma