Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes.

IF 4.8 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomolecules Pub Date : 2025-01-03 DOI:10.3390/biom15010057

Murali Ganesan, Anup S Pathania, Grace Bybee, Kusum K Kharbanda, Larisa Y Poluektova, Natalia A Osna

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引用次数: 0

Abstract

About 296 million people worldwide are living with chronic hepatitis B viral (HBV) infection, and outcomes to end-stage liver diseases are potentiated by alcohol. HBV replicates in hepatocytes, but other liver non-parenchymal cells can sense the virus. In this study, we aimed to investigate the regulatory effects of macrophages on HBV marker and interferon-stimulated genes (ISGs) expressions in hepatocytes. This study was performed on HBV-replicating HepG2.2.15 cells and human monocyte-derived macrophages (MDMs). We found that exposure of HepG2.2.15 cells to an acetaldehyde-generating system (AGS) increased HBV RNA, HBV DNA, and cccDNA expressions and suppressed the activation of ISGs, APOBEC3G, ISG15, and OAS1. Supernatants collected from IFNα-activated MDMs decreased HBV marker levels and induced ISG activation in AGS-treated and untreated HepG2.215 cells. These effects were reversed by exposure of MDMs to ethanol and mimicked by treatment with exosome release inhibitor GW4869. We conclude that exosome-mediated crosstalk between IFN-activated macrophages and HBV-replicating hepatocytes plays a protective role via the up-regulation of ISGs and suppression of HBV replication. However, ethanol exposure to macrophages breaks this protection.

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来源期刊

Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

3.60%

发文量

1640

审稿时长

18.28 days

期刊介绍： Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.