IL-8 exacerbates alcohol-induced fatty liver disease via the Akt/HIF-1α pathway in human IL-8-expressing mice

Abstract

Alcoholic fatty liver disease (AFLD) is a disease that causes liver damage due to chronic heavy drinking. AFLD is related to lipid accumulation in liver cells caused by alcohol intake. Interleukin-8 (IL-8) is an inflammatory cytokine associated with chemotaxis (deletion in mice) that has robust effects on the occurrence and development of disease by activating related signal transduction pathways to promote inflammation and cell proliferation. There is significantly increased IL-8 expression in liver disease, which may be related to the pathogenesis of AFLD. In this study, we used hydrodynamic injection to deliver the liver-specific expression vector pLIVE-hIL-8 into mice. We found that hIL-8 can exacerbate alcohol-induced fatty liver disease via the Akt/HIF-1α pathway. Exacerbated liver lipid degeneration in mice, which is characterized by excessive accumulation of triglycerides, and liver damage markers were significantly increased. Moreover, hIL-8 could increase the alcohol-induced release of ROS in fatty liver caused by alcohol and exacerbate fatty liver disease. The expression of liver lipid metabolism-related gene sterol regulatory element-binding protein-1c (SREBP-1c) was increased. Furthermore, the expression of peroxisome proliferator-activated receptor alpha (PPARα), which is related to liver fatty acid oxidation, was decreased. The findings obtained in this study of hIL-8 will help identify a potential target for the clinical treatment of AFLD.