ArticleGastroenterology2008
Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis.
Article in Gastroenterology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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Who cites it
138 citing papers in PubMed, 242 citations in OpenAlex.
- Article
- Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.The American journal of pathology · 2026Review
- Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease.Cellular & molecular immunology · 2025Review
- Liver immunology: Biological role and clinical significance.World journal of hepatology · 2025Review
- Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver.iScience · 2025Article
- A novel 11β-HSD1 inhibitor ameliorates liver fibrosis by inhibiting the notch signaling pathway and increasing NK cell population.Archives of pharmacal research · 2025Article
- Macrophage Evolution during Progression of Hepatitis Virus B-Related Acute-on-Chronic Liver Failure.Journal of innate immunity · 2025Article
- A multi-omics approach combining causal inference andFrontiers in immunology · 2025Article
- Review
- Liver fibrosis pathologies and potentials of RNA based therapeutics modalities.Drug delivery and translational research · 2024Review
- Role of immune cell interactions in alcohol-associated liver diseases.Liver research (Beijing, China) · 2024Review
- Effect of ethanol exposure on innate immune response in sepsis.Journal of leukocyte biology · 2024Review
- Immunopathogenesis of liver fibrosis in steatotic liver disease.Clinical and molecular hepatology · 2024Article
- Linking fatty liver diseases to hepatocellular carcinoma by hepatic stellate cells.Journal of the National Cancer Center · 2024Review
- Roles of innate lymphoid cells in metabolic and alcohol-associated liver diseases.JHEP reports : innovation in hepatology · 2024Review
- Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments.International journal of biological sciences · 2024Review
- Cytotoxic NK cells phenotype and activated lymphocytes are the main characteristics of patients with alcohol-associated liver disease.Clinical and experimental medicine · 2023Article
- Suppression of the antitumoral activity of natural killer cells under indirect coculture with cancer-associated fibroblasts in a pancreatic TIME-on-chip model.Cancer cell international · 2023Article
- Small-molecule chemical probes for the potential therapeutic targets in alcoholic liver diseases.Liver research (Beijing, China) · 2023Review
- Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles?Biomedicines · 2023Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsChronic alcohol drinking accelerates liver fibrosis in patients with viral hepatitis that cannot be fully explained by ethanol-enhanced liver damage. Here, we identified a novel mechanism by which alcohol accelerates liver fibrosis: inhibition of the antifibrotic effects of natural killer (NK) cells and interferon-gamma (IFN-gamma).
methodsAlcohol administration was achieved by feeding mice with a liquid diet containing 5% ethanol for 8 weeks. Liver fibrosis was induced by administration of carbon tetrachloride (CCl(4)) for 2 weeks. Hepatic stellate cells (HSCs) were also isolated and cultured for in vitro studies.
resultsCCl(4) treatment induced greater fibrosis and less apoptosis of HSCs in ethanol-fed mice compared with pair-fed mice. Polyinosinic-polycytidylic acid (Poly I:C) or IFN-gamma treatment inhibited liver fibrosis in pair-fed but not in ethanol-fed mice. Poly I:C activation of NK cell cytotoxicity against HSCs was attenuated in ethanol-fed mice compared with pair-fed mice, which was due to reduced natural killer group 2 member D (NKG2D), tumor necrosis factor-related apoptosis-inducing ligand, and IFN-gamma expression on NK cells from ethanol-fed mice. In vitro, HSCs from ethanol-fed mice were resistant to IFN-gamma-induced cell cycle arrest and apoptosis compared with pair-fed mice. Such resistance was due to diminished IFN-gamma activation of signal transducer and activator of transcription 1 (STAT1) in HSCs from ethanol-fed mice caused by the induction of suppressors of cytokine signaling proteins and the production of oxidative stress. Finally, HSCs from ethanol-fed mice were resistant to NK cell killing, which can be reversed by transforming growth factor-beta1 (TGF-beta1) neutralizing antibody.
conclusionsChronic ethanol consumption attenuates the antifibrotic effects of NK/IFN-gamma/STAT1 in the liver, representing new and different therapeutic targets with which to treat alcoholic liver fibrosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.