# IFN-β Overexpressing Adipose-Derived Mesenchymal Stem Cells Mitigate Alcohol-Induced Liver Damage and Gut Permeability

## TL;DR

Stem cells overexpressing interferon-beta reduce liver damage and gut leakiness caused by alcohol, likely through increased hepatocyte growth factor.

## Contribution

ASCs overexpressing IFN-β show protective effects against alcohol-induced liver injury and gut permeability via HGF.

## Key findings

- ASC-IFN-β reduced liver injury and inflammation in mice exposed to binge alcohol.
- ASC-IFN-β decreased gut leakiness as indicated by lower fecal albumin, blood endotoxin, and bacterial colony levels.
- HGF, but not IFN-β or TRAIL, mitigated ethanol-induced cell death and permeability in Caco-2 cells.

## Abstract

Alcoholic liver disease (ALD) is a form of hepatic inflammation. ALD is mediated by gut leakiness. This study evaluates the anti-inflammatory effects of ASCs overexpressing interferon-beta (ASC-IFN-β) on binge alcohol-induced liver injury and intestinal permeability. In vitro, ASCs were transfected with a non-viral vector carrying the human IFN-β gene, which promoted hepatocyte growth factor (HGF) secretion in the cells. To assess the potential effects of ASC-IFN-β, C57BL/6 mice were treated with three oral doses of binge alcohol and were administered intraperitoneal injections of ASC-IFN-β. Mice treated with binge alcohol and administered ASC-IFN-β showed reduced liver injury and inflammation compared to those administered a control ASC. Analysis of intestinal tissue from ethanol-treated mice administered ASC-IFN-β also indicated decreased inflammation. Additionally, fecal albumin, blood endotoxin, and bacterial colony levels were reduced, indicating less gut leakiness in the binge alcohol-exposed mice. Treatment with HGF, but not IFN-β or TRAIL, mitigated the ethanol-induced down-regulation of cell death and permeability in Caco-2 cells. These results demonstrate that ASCs transfected with a non-viral vector to induce IFN-β overexpression have protective effects against binge alcohol-mediated liver injury and gut leakiness via HGF.