Th17/Treg imbalance in triptolide-induced liver injury.
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.
Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Xinzhi
X
Wang
Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Zhenzhou
Z
Jiang
The Center Laboratory of Medicine, Maternity and Child Health Hospital, Zhenjiang 212001, PR China.
Weiping
W
Cao
Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Ziqiao
Z
Yuan
Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
LiXin
L
Sun
Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Jiangsu Provincial Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: lyzhang@cpu.edu.cn.
Luyong
L
Zhang
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000276:immunology*; D004224:Diterpenes / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000009:adverse effects; D005260:Female; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010616:Phenanthrenes / Q000009:adverse effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism
D004224:Diterpenes; D004852:Epoxy Compounds; C556062:IL10 protein, mouse; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D010616:Phenanthrenes; D014157:Transcription Factors; D016753:Interleukin-10; C001899:triptolide
Hepatotoxicity; Regulatory T cells; Th17 cells; Th17/Treg imbalance; Triptolide