Interleukin 10 inhibits oxidative stress-induced autophagosome formation in hepatic stellate cells by activating the mTOR-STAT3 pathway.

Exp Cell Res

Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, 29#Xinquan Road, Gulou District, Fuzhou, 350001, Fujian, China. Electronic address:

Published: February 2022

Autophagy is involved in the activation of hepatic stellate cells (HSCs) and liver fibrosis. Previous studies have shown that interleukin 10 (IL-10) has a marked therapeutic effect against liver fibrosis. However, few studies have evaluated the effect of IL-10 on autophagy in HSCs and fibrotic livers. The aim of this study was to assess the effect of IL-10 on the autophagy of HSCs in vitro and in vivo and then to explore the underlying pathway. In vitro, The results revealed that IL-10 had inhibitory effects on hydrogen peroxide (HO)-induced autophagy, as evidenced by the decreased LC3II/I ratio and Beclin1 expression, increased p62 expression, reduced numbers of autophagosomes, and blocked autophagy initiation in HSCs. Mechanistically, IL-10 significantly promoted the phosphorylation of the signal transducer and activator of transcription 3(STAT3) and mammalian target of rapamycin (mTOR), leading to the activation of STAT3 and mTOR, which in turn inhibited autophagy. In vivo, the increased expression of IL-10 in fibrotic livers inhibited significantly liver fibrosis and decreased the autophagic activity in fibrotic livers and HSCs. Overall, our results indicate that IL-10 suppressed HO-induced autophagy in HSCs by activating the STAT3-mTOR signaling pathway. Present study provides a new theoretical basis for the anti-fibrotic effects of IL-10.

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http://dx.doi.org/10.1016/j.yexcr.2021.113001DOI Listing

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