ArticleMolecular immunology2016
Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice.
Article in Molecular immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026Review
- Research progress on the roles of complement in liver injury.World journal of hepatology · 2025Review
- Role of Complement in Liver Diseases.Seminars in liver disease · 2024Review
- Emerging concepts in alcohol, infection & immunity: A summary of the 2023 alcohol and immunology research interest group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2024Article
- The role of C5aR1-mediated hepatic macrophage efferocytosis in NASH.Scientific reports · 2024Article
- Profiling the oxylipidome in aged mice after chronic ethanol feeding: Identifying lipid metabolites as drivers of hepatocyte stress.Alcohol (Fayetteville, N.Y.) · 2023Article
- Article
- Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.Annual review of pathology · 2023Review
- Polydeoxyribonucleotide ameliorates alcoholic liver injury though suppressing phosphatidylinositol 3-kinase/protein kinase B signaling pathway in mice.Journal of exercise rehabilitation · 2022Article
- A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- MyD88 in hepatic stellate cells promotes the development of alcoholic fatty liver via the AKT pathway.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Transcriptomics reveals immune-metabolism disorder in acute-on-chronic liver failure in rats.Life science alliance · 2022Article
- 3'mRNA sequencing reveals pro-regenerative properties of c5ar1 during resolution of murine acetaminophen-induced liver injury.NPJ Regenerative medicine · 2022Article
- Immunological mechanisms and therapeutic targets of fatty liver diseases.Cellular & molecular immunology · 2021Review
- Roles of the complement system in alcohol-induced liver disease.Clinical and molecular hepatology · 2020Review
- Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption.Scientific reports · 2020Article
- Inflammatory pathways in alcoholic steatohepatitis.Journal of hepatology · 2019Review
- Complement Factor D protects mice from ethanol-induced inflammation and liver injury.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Anaphylatoxin Receptors C3aR and C5aR1 Are Important Factors That Influence the Impact of Ethanol on the Adipose Secretome.Frontiers in immunology · 2018Article
- Hepatocyte-derived macrophage migration inhibitory factor mediates alcohol-induced liver injury in mice and patients.Journal of hepatology · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundComplement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known.
methodsC57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32%kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFα, and C5a.
resultsChronic ethanol feeding increased expression of pro-inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid-specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFα, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFα was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFα.
conclusionTaken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol-induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding.
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