IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease.

ABSTRACT:

Background & aims

Chronic alcohol consumption is a leading risk factor for the development of hepatocellular carcinoma (HCC), which is associated with a marked increase in hepatic expression of pro-inflammatory IL-17A and its receptor IL-17RA.

Methods

Genetic deletion and pharmacological blocking were used to characterize the role of IL-17A/IL-17RA signaling in the pathogenesis of HCC in mouse models and human specimens.

Results

We demonstrate that the global deletion of the Il-17ra gene suppressed HCC in alcohol-fed diethylnitrosamine-challenged Il-17ra^-/- and major urinary protein-urokinase-type plasminogen activator/Il-17ra^-/- mice compared with wild-type mice. When the cell-specific role of IL-17RA signaling was examined, the development of H

SUBMITTER: Ma HY 

PROVIDER: S-EPMC7167339 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature