Activation of natural killer T cells contributes to triptolide-induced liver injury in mice

Acta Pharmacologica Sinica
Xin-Zhi WangZhenzhou Jiang

Abstract

Triptolide (TP) is the main active ingredient of Tripterygium wilfordii Hook.f, which has attracted great interest due to its promising efficacy for autoimmune diseases and tumors. However, severe adverse reactions, especially hepatotoxicity, have restricted its approval in the market. In the present study we explored the role of hepatic natural killer T (NKT) cells in the pathogenesis of TP-induced liver injury in mice. TP (600 μg/kg/day, i.g.) was administered to female mice for 1, 3, or 5 days. We found that administration of TP dose-dependently induced hepatotoxicity, evidenced by the body weight reduction, elevated serum ALT and AST levels, as well as significant histopathological changes in the livers. However, the mice were resistant to the development of TP-induced liver injury when their NKT cells were depleted by injection of anti-NK1.1 mAb (200 μg, i.p.) on days -2 and -1 before TP administration. We further revealed that TP administration activated NKT cells, dominantly releasing Th1 cytokine IFN-γ, recruiting neutrophils and macrophages, and leading to liver damage. After anti-NK1.1 injection, however, the mice mainly secreted Th2 cytokine IL-4 in the livers and exhibited a significantly lower percentage of hepatic...Continue Reading

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Citations

Sep 29, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mengzhi ZouXinzhi Wang
Dec 10, 2020·Medicinal Research Reviews·Yanqiong ZhangNa Lin
Oct 19, 2019·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Liang MaJian-Ping Chen

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
PCR
electrophoresis
pharmacotherapy

Software Mentioned

FlowJo

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