Tumor progression locus 2 deletion attenuates alcohol‐induced hepatic inflammatory foci and cytokine expression in mice

Abstract

The pathogenesis of alcohol‐induced fatty liver disease involves the interaction of several inflammatory signaling pathways. Tumor progression locus 2 (TPL2) is a kinase that functions as a critical regulator of inflammatory pathways by up‐regulating production of inflammatory cytokines. The present study aims to fill the gap in knowledge regarding the involvement of TPL2 in the mechanism of alcohol‐induced hepatic inflammation. In this study, male TPL2 knockout (TPL2KO) mice and wild‐type (WT) mice were pair‐fed with Lieber‐DeCarli liquid diet (LD) or alcoholic liquid diet (ALD, 27% energy from ethanol) for 4 weeks. Results show that the deletion of TPL2 significantly reduced inflammatory foci in the liver of mice consuming both LD and ALD as compared to their respective WT controls. This reduction was associated with suppression of hepatic inflammatory gene expression of interleukin‐6, tumor necrosis factor‐α, and interleukin‐1β. Histological analysis of livers showed TPL2 deletion significantly decreased steatosis in mice fed LD, but not in mice fed ALD, as compared to their respective WT controls. The demonstration that TPL2 deletion attenuates alcohol‐induced hepatic inflammation provides evidence for a novel role for TPL2 in the pathogenesis of alcohol‐induced fatty liver disease.Grant Funding Source : NIDDK RO1‐DK‐082574/USDA 1950‐51000‐064S