IL‐6 Trans‐Signaling Plays Important Protective Roles in Acute Liver Injury Induced by Acetaminophen in Mice |
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| Authors: | San‐Qiang Li Sha Zhu Hong‐Mei Han Hua‐Jie Lu Hong‐Ye Meng |
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| Affiliation: | 1. The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China;2. Department of Microbiology Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China |
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| Abstract: | Our study was undertaken to evaluate the important role of interleukin‐6 (IL‐6) trans‐signaling in acetaminophen (AAP)‐induced liver injury. A soluble gp130 protein (sgp130Fc) exclusively inhibits IL‐6 trans‐signaling, whereas an IL‐6/soluble IL‐6 receptor (sIL‐6R) fusion protein (hyper‐IL‐6) mimics IL‐6 trans‐signaling. Using these tools, we investigated the role of IL‐6 trans‐signaling in AAP‐induced liver injury. Blockade of IL‐6 trans‐signaling during AAP‐induced liver injury remarkably increased the levels of serum aspartate aminotransferase and alanine aminotransferase; lowered the level of serum sIL‐6R; aggravated liver injury; inhibited the expression of phosphorylation of STAT3 (pSTAT3), proliferating cell nuclear antigen, vascular endothelial growth factor, and glycogen synthesis; and induced the expression of Caspase3, cytochrome P450 2E1 (CYP2E1), and hepatocyte apoptosis in the liver of mice. In summary, our study suggested that IL‐6 trans‐signaling plays important protective roles by regulating the hepatocyte proliferation and apoptosis, angiogenesis, CYP2E1 expression, and glycogen metabolism during AAP‐induced liver injury in mice. |
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| Keywords: | IL‐6 trans‐signaling Acetaminophen sgp130Fc Hyper‐IL‐6 |
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