The study was designed to investigate the immune-modulatory effects of triptolide (TP) on CD4(+) T cell responses during liver injury. Previous studies have suggested that TP plays a critical role in modulating both innate and adaptive immune reactions, but its effects on the Th17/Treg balance during TP-induced liver injury remain unknown. In this study, female C57BL/6 mice were administered by oral gavage with TP at a dose of 250 or 500 μg/kg per mouse. We examined the plasma biochemical parameters, histopathological changes, hepatic frequencies of Th17 cells and Treg cells, hepatic expression of transcriptional factors and cytokine genes and hepatic interleukin (IL)-17 and IL-10 levels in TP-administered mice. Mice treated with TP displayed liver injury with markedly increased plasma transaminase as well as hepatic mRNA expression of retinoid related orphan receptor (ROR)-γt and hepatic IL-17 level at 24h. However, hepatic frequencies of Tregs and hepatic expression of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) decreased at 24h after TP administration. Furthermore, we found that elevated serum biochemical parameters positively correlated with the Th17/Treg ratios. Taken together, these results revealed a novel and interesting phenomenon of TP in the enhancement of the expansion of Th17 cells and suppression of the production of Tregs during liver injury, which may represent a new pathogenesis of TP-induced liver injury.
Keywords: Hepatotoxicity; Regulatory T cells; Th17 cells; Th17/Treg imbalance; Triptolide.
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