The role of neutrophils in triptolide-induced liver injury.
10.1016/S1875-5364(18)30105-5
- Author:
Xin-Zhi WANG
1
;
Shen-Ye ZHANG
2
;
Yao XU
1
;
Lu-Yong ZHANG
3
,
4
;
Zhen-Zhou JIANG
3
,
5
Author Information
1. Jiangsu Key Laboratory of Drug Screening, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
2. Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
3. Jiangsu Key Laboratory of Drug Screening, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China
4. Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009, China. Electronic address: lyzhang@cpu.edu.cn.
5. Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research, Nanjing 210009, China. Electronic address: beaglejiang@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Depletion;
Inflammatory response;
Liver injury;
Neutrophil;
Triptolide
- MeSH:
Animals;
Chemical and Drug Induced Liver Injury;
etiology;
immunology;
Chemokine CCL2;
genetics;
immunology;
Diterpenes;
adverse effects;
Drugs, Chinese Herbal;
adverse effects;
Epoxy Compounds;
adverse effects;
Female;
Humans;
Interleukin-6;
genetics;
immunology;
Intracellular Signaling Peptides and Proteins;
genetics;
immunology;
Liver;
drug effects;
immunology;
Mice;
Mice, Inbred C57BL;
Neutrophil Infiltration;
drug effects;
Neutrophils;
drug effects;
immunology;
Phenanthrenes;
adverse effects;
Tripterygium;
adverse effects;
chemistry;
Tumor Necrosis Factor-alpha;
genetics;
immunology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2018;16(9):653-664
- CountryChina
- Language:English
-
Abstract:
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 C57BL/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 CD11b, 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.
