The role of neutrophils in triptolide-induced liver injury

作     者：WANG Xin-Zhi ZHANG Shen-Ye XU Yao ZHANG Lu-Yong JIANG Zhen-Zhou 

作者机构：Jiangsu Key Laboratory of Drug Screening Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University Nanjing 210009 China Faculty of Health and Medical Science University of Copenhagen Copenhagen Denmark Key Laboratory of Drug Quality Control and Pharmacovigilance China Pharmaceutical University Ministry of Education Nanjing 210009 China Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research Nanjing 210009 China 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2018年第16卷第9期

页      面：653-664页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Nos.81703626,81773995,81773827,81573514,81673684,81673443,81573690,81173651,and 81320108029) the Fundamental Research Funds for the Central Universities(No.2632017PY11) the Natural Science Foundation of Jiangsu Province(No.BK20151439) the College Students Innovation Project for the R&D of Novel Drugs(No.J1310032) 

主　　题：Triptolide Liver injury Inflammatory response Neutrophil Depletion 

摘      要：Triptolide(TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57 BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11 b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.