IL-6 trans-signaling plays important protective roles in acute liver injury induced by acetaminophen in mice.
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.
The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China. sanqiangli2001@163.com.
San-Qiang
SQ
Li
Department of Microbiology Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 45001, People's Republic of China.
Sha
S
Zhu
The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
Hong-Mei
HM
Han
The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
Hua-Jie
HJ
Lu
The Molecular Medicine Key Laboratory of Liver Injury and Repair, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
Hong-Ye
HY
Meng
D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008807:Mice, Inbred BALB C; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D000082:Acetaminophen; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D000093242:Interleukin-6 Inhibitors; C577686:interleukin-6, mouse; C519852:olamkicept
Acetaminophen; Hyper-IL-6; IL-6 trans-signaling; sgp130Fc