Interleukin-9 attenuates inflammatory response and hepatocyte apoptosis in alcoholic liver injury

• DOI: 10.1016/j.lfs.2021.120180
• Publication Date: 2021-11-26T16:22:45Z
• Authors: Hongwu Meng; Ruowen Niu; Hongmei You; Ling Wang; Rui Feng; Cheng Huang; Jun Li
• Keywords: Male; STAT3 Transcription Factor; 0301 basic medicine; Ethanol; Macrophages; Interleukin-9; Central Nervous System Depressants; Apoptosis; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Hepatocytes; Animals; Chemical and Drug Induced Liver Injury

Alcoholic liver injury is a liver cell dysfunction disease caused by long-term or excessive alcohol consumption. Inhibiting the production of inflammatory factors is an important way to alleviate liver injury. Interleukin-9 (IL-9) is one of the members of IL-2Rγc family. It has multiple biological functions. Previous studies have shown that IL-9 is a cytokine that is closely related to inflammatory disease, allergic diseases, autoimmune diseases, and parasitic infections. However, no systematic studies have been performed to address the role of IL-9 in ALI. This project aims to investigate the effects of IL-9 on macrophage-related inflammatory response and hepatocyte apoptosis in alcohol-induced liver injury by injecting adeno-associated virus (AAV9) into tail vein. In the ALI model group, western blot and ELISA assays demonstrated that the expression of IL-9 was reduced. Overexpression of IL-9 relieved the injury and reduced the serum levels of IL-6, TNF-α in EtOH-induced ALI mouse model. Moreover, by using western blot, it was indicated that IL-9 can inhibit the expression of pro-apoptotic protein, such as cleaved caspase 3 and Bax. In vitro, mouse recombinant protein IL-9 inhibited the expression of IL-6, TNF-α in EtOH-induced RAW264.7 cells. Moreover, flow cytometry and western blot results displayed that macrophage-derived IL-9 inhibited hepatocyte apoptosis. After silencing STAT3 in AML-12 cells, the anti-apoptotic effect of macrophage-derived IL-9 was further enhanced. These results indicate that IL-9 reduces the production of pro-inflammatory factors in ALI. Furthermore, macrophage-derived IL-9 can reduce hepatocyte apoptosis by inhibiting the activation of the STAT3 pathway.