Qili Wu1, Jingrou Chen1, Xiaoli Hu2, Yinhong Zhu1, Shujuan Xie1, Changyou Wu3, Zhong Pei4, Shiqiu Xiong5, Yanwen Peng1. 1. The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China. 2. Department of Operative Dentistry and Endodontics, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, PR China. 3. Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China. 4. Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China. 5. Cell Biology group, National Measurement Lab, LGC, Fordham, Cambridgeshire, UK.
Abstract
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-induced acute liver injury, which suggests the potential therapeutic application of Areg in immune-mediated ALF.
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-induced acute liver injury, which suggests the potential therapeutic application of Areg in immune-mediated ALF.
Entities:
Keywords:
Amphiregulin (Areg); IL-22; STAT3; acute liver failure (ALF); concanavalin A (Con A)
Authors: Jonathan Florentin; Jingsi Zhao; Yi-Yin Tai; Wei Sun; Lee L Ohayon; Scott P O'Neil; Anagha Arunkumar; Xinyi Zhang; Jianhui Zhu; Yassmin Al Aaraj; Annie Watson; John Sembrat; Mauricio Rojas; Stephen Y Chan; Partha Dutta Journal: Life Sci Alliance Date: 2022-06-22