IL-22 relieves hepatic ischemia-reperfusion injury by inhibiting mitochondrial apoptosis based on the activation of STAT3

Abstract

Introduction: Interleukin-22 (IL-22) has been proven to exhibit a protective role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to explore the change of IL-22 and IL-22 receptor 1 (IL-22R1) axis in HIRI and its role in mitochondrial apoptosis associated with STAT3 activation.

Materials and methods: I/R mice were examined for the expression of IL-22, IL-22R1 and IL-22BP. The roles of IL-22 in hepatic histopathology and oxidative stress injuries (ALT, MDA and SOD) were determined. Oxidative stress damages of AML-12 cells were induced by H₂O₂, and were indicated by apoptosis, Ca²⁺ concentration, and mitochondrial function. The effects of IL-22 on p-STAT3^Try705 were analyzed.

Results: We found that the expression of IL-22, IL-22R1, and IL-22BP was elevated 24 h after I/R induction, while decreased 48 h after I/R induction. Furthermore, we also discovered that IL-22 rescued the morphological damages and dysfunction of hepatocytes induced by H₂O₂, which were antagonized by IL-22BP, an endogenous antagonist of IL-22. Additionally, increased levels of Ca²⁺ concentration, MDA, ROS, apoptosis and mitochondrial dysfunction were noticed in H₂O₂-treated hepatocytes. However, IL-22 ameliorated the effects of I/R or H₂O₂. The protective effects of IL-22 were reversed by AG490, a specific antagonist of STAT3.

Conclusions: In conclusion, our results indicated that IL-22 inhibited I/R-induced oxidative stress injury, Ca²⁺ overload, and mitochondrial apoptosis via STAT3 activation.

Keywords: Hepatic ischemia-reperfusion injury; IL-22; IL-22R1; Mitochondrial dysfunction; STAT3.