Amphiregulin alleviated concanavalin A-induced acute liver injury via IL-22

作者：Qili Wu, Jingrou Chen, Xiaoli Hu, Yinhong Zhu, Shu‐Juan Xie, Changyou Wu, Zhong Pei, Shiqiu Xiong, Yanwen Peng · 发表于：Immunopharmacology and Immunotoxicology · 年份：2020 · DOI：10.1080/08923973.2020.1810271 · 被引用次数：8 · 研究领域：Cytokine Signaling Pathways and Interactions、Psoriasis: Treatment and Pathogenesis、Virus-based gene therapy research

Objectives Amphiregulin (Areg), a glycoprotein from the epidermal growth factor receptor (EGFR) ligand family, has a well-documented protective role against tissue injury; however, its effects on immune-mediated liver injury are still unclear. Here, we used a concanavalin A (ConA)-induced acute liver hepatitis model to explore the effects of Areg on immune-mediated acute liver injury.Materials and methods Some C57BL/6 mice were administered ConA at a dose of 20 mg/kg (model mice), and some received 5 µg of Areg (treated mice). Then, their survival rates over 36 h were analyzed. After 5 h of treatment, liver function, hepatic histology, and apoptosis in liver tissue were investigated, and cytokine expression and neutrophil infiltration and activity in the liver were detected. Moreover, the protective effects of Areg were also evaluated without IL-22 in vivo.Results Our results showed that Areg administration increased acute liver failure (ALF) mouse survival, restored liver function, and alleviated liver damage. Interestingly, Areg administration increased IL-22 production in hepatic T cells and upregulated IL-22 concentrations in the serum and liver, whereas IL-22 neutralization completely abolished the therapeutic effect of Areg. Meanwhile, Areg administration was concomitant with increased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, which are important in the hepatoprotective mechanism of IL-22.Conclusions Areg showed direct protective effects against ConA-i...