title: Interleukin-17 mediates triptolide-induced liver injury in mice.
abstract: Triptolide (TP)-induced liver injury can be attributed to the Th17/Treg imbalance with the enhancement of the expansion of Th17 cells and suppression of the production of Tregs, especially the significant increase of interleukin (IL)-17 secreted by helper T (Th) 17 cells. To further investigate the involvement of IL-17-mediated immune response in the TP-induced hepatotoxicity, we examined the plasma transaminase, histopathological changes, hepatic frequencies of Th17 cells, hepatic expression of transcriptional factors and cytokines genes and plasma IL-17 levels after administration of TP (600 μg/kg) by oral gavage to female C57BL/6 mice. Mice treated with TP displayed acute liver injury with significantly increased hepatic frequencies of Th17 cells, mRNA expression of retinoid-related orphan receptor (ROR)-γt and plasma IL-17 level as well as the plasma ALT and AST. Neutralization study using anti-IL-17 antibody ameliorated TP-induced liver injury. In contrast, when challenged by coadministration of recombinant IL-17, hepatotoxicity was exacerbated in the triptolide-administered mice. In summary, this report was demonstrated for the first time that IL-17-mediated immune response is involved in the pathogenesis of TP-induced liver injury in mice, which may shed light on the mechanisms of TP-induced liver injury.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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. Electronic address: jiangcpu@163.com.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Pathology, University of Illinois at Chicago, 909 S. Wolcott St., Chicago, IL 60612, United States.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; School of Pharmacy, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, PR China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Su
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D004224:Diterpenes / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D004852:Epoxy Compounds / Q000633:toxicity; D005260:Female; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010616:Phenanthrenes / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018925:Chemokines; D016207:Cytokines; D017931:DNA Primers; D004224:Diterpenes; D004852:Epoxy Compounds; D020381:Interleukin-17; D010616:Phenanthrenes; C001899:triptolide
keywords: Drug-induced liver injury; IL-17; Neutrophils; Triptolide