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Interleukin ‐ 17 ‐ mediated immune responses in triptolide ‐ induced liver injury in mice (LB637)
Author(s) -
Wang Xinzhi,
Jiang Zhenzhou,
Zhang Luyong
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb637
Subject(s) - immune system , liver injury , triptolide , pathogenesis , immunology , hepatocyte , interleukin 17 , medicine , interleukin , tumor necrosis factor alpha , cytokine , biology , pharmacology , apoptosis , in vitro , biochemistry
The mechanisms of drug ‐ induced liver injury (DILI) have not been fully claried. Many factors, including oxidative stress and hepatic immune response, can contribute to the pathogenesis of DILI. Interleukin (IL) ‐ 17 secreted by helper T (Th) 17 cells are critical components of immune response in DILI. Triptolide (TP) has been reported to induce hepatocyte damage with inflammatory cells inltration in the liver. To 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 oral administration of TP (600 μg/kg) to female C57BL/6 mice for 24 h. Mice treated with TP displayed acute liver injury with signicantly 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 co ‐ administration 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. Grant Funding Source : Supported by National Natural Science Foundation of ChinaNo. No.81173651