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

• Published in: Immunopharmacology and immunotoxicology 2020-09, Vol.42 (5), p.473-483
• Main Authors: Wu, Qili, Chen, Jingrou, Hu, Xiaoli, Zhu, Yinhong, Xie, Shujuan, Wu, Changyou, Pei, Zhong, Xiong, Shiqiu, Peng, Yanwen
• Format: Article
• Language: English
• Subjects: acute liver failure (ALF); Amphiregulin (Areg); Amphiregulin - pharmacology; Animals; Apoptosis - drug effects; bcl-X Protein - metabolism; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - prevention & control; Concanavalin A; concanavalin A (Con A); Disease Models, Animal; IL-22; Interleukin-22; Interleukins - metabolism; Liver - drug effects; Liver - immunology; Liver - metabolism; Liver - pathology; Liver Failure, Acute - chemically induced; Liver Failure, Acute - immunology; Liver Failure, Acute - metabolism; Liver Failure, Acute - prevention & control; Mice, Inbred C57BL; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal Transduction; STAT3; STAT3 Transcription Factor - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1080/08923973.2020.1810271

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. 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. 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. Areg showed direct protective effects against ConA-induced acute liver injury, which suggests the potential therapeutic application of Areg in immune-mediated ALF.