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Triptolide attenuates oxidative stress, NF-κB activation and multiple cytokine gene expression in murine peritoneal macrophage
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2006
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Inos MrnaInnate Immune SystemImmunologyImmune RegulationCell DeathOxidative StressInflammationStimulated Murine MacrophagesCell SignalingMacrophage BiologyAllergyAutoimmune DiseaseChronic InflammationAutoimmunityImmune FunctionCell BiologyPhagocyteCytokineAnti-inflammatoryImmune Cell DevelopmentMathematical ModelNf-κb ActivationMedicineMurine Peritoneal Macrophage
Triptolide is a natural, biologically active compound extracted from the Chinese herb Tripterygium Wilfordii hook, that possesses potent immunosuppressive properties. In the course of our study, we examined the effects of triptolide on stimulated murine macrophages and demonstrated that triptolide inhibited superoxide anion production, NO production, and the expression of iNOS mRNA and the mRNA of some key inflammation-related cytokines, namely TNF-alpha, IL-1beta, IL-6 and IFN-gamma. This inhibition was accompanied by the inhibition of nuclear transcription factor NF-kappaB activation. We further developed a mathematical model to simulate interplay between triptolide, ROS, NF-kappaB, iNOS and related cytokines. Our results suggest that triptolide acts to regulate inflammation through NF-kappaB-mediated inhibition of inflammation-related cytokines and the production of superoxide anion and NO.