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 / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>