Th17/Treg imbalance in triptolide-induced liver injury

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• 作者：Xinzhi Wang ; Zhenzhou Jiang ; Weiping Cao ; Ziqiao Yuan ; LiXin Sun ; Luyong Zhang
• 关键词：Th17 cells ; T helper 17 cells ; Treg cells ; regulatory T cells ; ROR纬t ; retinoid orphan nuclear receptor 纬t ; FoxP3 ; forkhead/winged-helix family transcriptional repressor p3 ; ELISA ; enzyme linked immunosorbent assay ; IL-17 ; interleukin-17 ; TP ; triptolide ; TWHF ; Tripterygium wilfordii Hook F ; TGF-尾 ; transforming growth factor-尾 ; ALT ; alanine transaminase ; AST ; aspartate transaminase ; GGT ; 纬-glutamyl transpeptidase ; TBIL ; total bilirubin ; CHO ; cholesterol ; H&E ; hematoxylin and eosin
• 刊名：Fitoterapia
• 出版年：March, 2014
• 年：2014
• 卷：93
• 期：Complete
• 页码：245-251
• 全文大小：1175 K

文摘

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 渭g/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)-纬t and hepatic IL-17 level at 24 h. However, hepatic frequencies of Tregs and hepatic expression of forkhead/winged-helix family transcriptional repressor p3 (FoxP3) decreased at 24 h 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.