IL-22 relieves sepsis-induced liver injury via activating JAK/STAT3 signaling pathway

Abstract

The purpose of this study was to investigate the influence of interleukin(IL)-22 on the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway and sepsis-induced liver injury in rats. A total of 48 Sprague-Dawley rats were randomly divided into sham-operated group (n=12), model group (n=12), low-dose group (n=12) and high-dose group (n=12). Next, rat models of sepsis-induced liver injury were established through cecal ligation and puncture (CLP). At 12 h after surgery, blood was collected by heart puncture to detect liver function of the rats. It was found that the activity of alanine aminotransferase (ALT) and aspartame aminotransferase (AST) and the content of total bilirubin were reduced in low-dose group and high-dose group. Hematoxylin-eosin (HE) staining results revealed that after treatment with IL-22, the liver injury was relieved compared with model group. Moreover, the results of TUNEL staining assay revealed that the apoptosis level of liver cells declined after treatment with IL-22. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the levels of IL-6 and TNF-α were reduced, while the level of IL-10 was increased after treatment with IL-22. Moreover, it was discovered that the SOD content was overtly elevated in low-dose and high-dose groups compared with that in the model group. Finally, using Western blotting, it was confirmed that in comparison with the model group, the levels of Bcl-2/Bax and JAK/STAT3 signaling pathway-related proteins were markedly raised, while the level of Caspase-3 was decreased in the low-dose and high-dose groups. In conclusion, IL-22 can improve liver function, reduce the apoptosis level of liver cells, the expression of apoptosis-related proteins and the release of inflammatory factors, and alleviate liver injury by activating the JAK/STAT3 signaling pathway.

Keywords: IL-22; JAK/STAT3 signaling pathway; liver injury; sepsis.