ArticleJournal of leukocyte biology2017
Alcohol-induced miR-155 and HDAC11 inhibit negative regulators of the TLR4 pathway and lead to increased LPS responsiveness of Kupffer cells in alcoholic liver disease.
Article in Journal of leukocyte biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 85 citations in OpenAlex.
- [Histone deacetylases and alcohol-related liver disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Novel Vascularized Human Liver Organoids for Modeling Alcohol-Induced Liver Injury and Developing Hepatoprotective Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microbiome modulation as a therapeutic strategy for alcohol-induced gut dysbiosis and associated disorders.Antonie van Leeuwenhoek · 2025Review
- Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease.Cellular & molecular immunology · 2025Review
- Myeloid-derived MANF ameliorates ethanol-induced liver injury by enhancing microRNA-223 expression.Journal of gastroenterology · 2025Article
- Review
- Immunology and treatments of fatty liver disease.Archives of toxicology · 2025Review
- Noncoding RNA and Alcohol Use Disorder: A Scoping Review of Current Research and Knowledge Gaps.Alcohol research : current reviews · 2025Article
- Molecular regulators of alcoholic liver disease: a comprehensive analysis of microRNAs and long non-coding RNAs.Frontiers in medicine · 2025Review
- microRNAs and Other Serological Markers of Liver Fibrosis in Patients with Alcohol-Related Liver Cirrhosis.Biomedicines · 2024Article
- Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.Biomolecules · 2024Review
- MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?Cancers · 2023Review
- Fatty Liver Disease, Metabolism and Alcohol Interplay: A Comprehensive Review.International journal of molecular sciences · 2023Review
- MicroRNAs in Macrophages: Regulators of Activation and Function.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Unraveling the Complex Interplay between Epigenetics and Immunity in Alcohol-Associated Liver Disease: A ComprehensiveInternational journal of biological sciences · 2023Review
- The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review).Sovremennye tekhnologii v meditsine · 2023Review
- Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4.Clinical and molecular hepatology · 2022Article
- MiR155 Disrupts the Intestinal Barrier by Inducing Intestinal Inflammation and Altering the Intestinal Microecology in Severe Acute Pancreatitis.Digestive diseases and sciences · 2022Article
- Epigenetics of alcohol-related liver diseases.JHEP reports : innovation in hepatology · 2022Review
- Profiling of extracellular vesicle-bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates.Alcoholism, clinical and experimental research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Inflammation promotes the progression of alcoholic liver disease. Alcohol sensitizes KCs to gut-derived endotoxin (LPS); however, signaling pathways that perpetuate inflammation in alcoholic liver disease are only partially understood. We found that chronic alcohol feeding in mice induced miR-155, an inflammatory miRNA in isolated KCs. We hypothesized that miR-155 might increase the responsiveness of KCs to LPS via targeting the negative regulators of LPS signaling. Our results revealed that KCs that were isolated from alcohol-fed mice showed a decrease in IRAK-M, SHIP1, and PU.1, and an increase in TNF-α levels. This was specific to KCs, as no significant differences were observed in these genes in hepatocytes. We found a causal effect of miR-155 deficiency on LPS responsiveness, as KCs that were isolated from miR-155 KO mice showed a greater induction of IRAK-M, SHIP1, and suppressor of cytokine signaling 1 after LPS treatment. C/EBPβ, a validated miR-155 target, stimulates IL-10 transcription. We found a higher induction of C/EBPβ and IL-10 in KCs that were isolated from miR-155 KO mice after LPS treatment. Gain- and loss-of-function studies affirmed that alcohol-induced miR-155 directly regulates IRAK-M, SHIP1, suppressor of cytokine signaling 1, and C/EBPβ, as miR-155 inhibition increased and miR-155 overexpression decreased these genes in LPS or alcohol-pretreated wild-type KCs. HDAC11, a regulator of IL-10, was significantly increased and IL-10 was decreased in KCs that were isolated from alcohol-fed mice. Functionally, knockdown of HDAC11 with small interfering RNA resulted in an IL-10 increase in LPS or alcohol-pretreated Mϕ. We found that acetaldehyde and NF-κB pathways regulate HDAC11 levels. Collectively, our results indicate that the alcohol-induced responsiveness of KCs to LPS, in part, is governed by miR-155 and HDAC11.
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Registered trials
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.