Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes
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 regu...
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2025-01-01
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| author | Murali Ganesan Anup S. Pathania Grace Bybee Kusum K. Kharbanda Larisa Y. Poluektova Natalia A. Osna |
| author_facet | Murali Ganesan Anup S. Pathania Grace Bybee Kusum K. Kharbanda Larisa Y. Poluektova Natalia A. Osna |
| author_sort | Murali Ganesan |
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| description | 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, <i>APOBEC3G</i>, <i>ISG15</i>, and <i>OAS1</i>. 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. |
| format | Article |
| id | doaj-art-2303c5cca6c6439b80c9f2afeb7ccc20 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-2303c5cca6c6439b80c9f2afeb7ccc202025-01-24T13:25:01ZengMDPI AGBiomolecules2218-273X2025-01-011515710.3390/biom15010057Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected HepatocytesMurali Ganesan0Anup S. Pathania1Grace Bybee2Kusum K. Kharbanda3Larisa Y. Poluektova4Natalia A. Osna5Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USAAbout 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, <i>APOBEC3G</i>, <i>ISG15</i>, and <i>OAS1</i>. 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.https://www.mdpi.com/2218-273X/15/1/57HBVmacrophageshepatocytesethanolinterferon-stimulated genes |
| spellingShingle | Murali Ganesan Anup S. Pathania Grace Bybee Kusum K. Kharbanda Larisa Y. Poluektova Natalia A. Osna Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes Biomolecules HBV macrophages hepatocytes ethanol interferon-stimulated genes |
| title | Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes |
| title_full | Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes |
| title_fullStr | Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes |
| title_full_unstemmed | Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes |
| title_short | Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes |
| title_sort | ethanol disrupts the protective crosstalk between macrophages and hbv infected hepatocytes |
| topic | HBV macrophages hepatocytes ethanol interferon-stimulated genes |
| url | https://www.mdpi.com/2218-273X/15/1/57 |
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