ArticleJournal of immunology (Baltimore, Md. : 1950)2018
Human Binge Alcohol Intake Inhibits TLR4-MyD88 and TLR4-TRIF Responses but Not the TLR3-TRIF Pathway: HspA1A and PP1 Play Selective Regulatory Roles.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Dexamethasone activates anti-tumor immunity in multiple myeloma by dismantling the GR-PPP1CB complex to restore STING/IRF3 signaling.Journal for immunotherapy of cancer · 2026Article
- Knockdown of Tlr3 in dorsal striatum reduces ethanol consumption and acute functional tolerance in male mice.Brain, behavior, and immunity · 2024Article
- Exploring the Action Mechanism and Validation of the Key Pathways ofCombinatorial chemistry & high throughput screening · 2024Article
- Alcohol, White Adipose Tissue, and Brown Adipose Tissue: Mechanistic Links to Lipogenesis and Lipolysis.Nutrients · 2023Review
- Prenatal and adolescent alcohol exposure programs immunity across the lifespan: CNS-mediated regulation.Pharmacology, biochemistry, and behavior · 2022Review
- Blood and brain gene expression signatures of chronic intermittent ethanol consumption in mice.PLoS computational biology · 2022Article
- Immune treatments for alcohol use disorder: A translational framework.Brain, behavior, and immunity · 2021Review
- The Prophylactic Effects of Glutamine on Muscle Protein Synthesis and Degradation in Rats with Ethanol-Induced Liver Damage.Nutrients · 2021Article
- Deletion of Tlr3 reduces acute tolerance to alcohol and alcohol consumption in the intermittent access procedure in male mice.Addiction biology · 2021Article
- Frutescone O fromFrontiers in pharmacology · 2021Article
- Acute Alcohol Intoxication Modulates Monocyte Subsets and Their Functions in a Time-Dependent Manner in Healthy Volunteers.Frontiers in immunology · 2021Article
- Harnessing the Proteostasis Network in Alcohol-associated Liver Disease.Current pathobiology reports · 2020Article
- Article
- Mitochondrial Double-Stranded RNA in Exosome Promotes Interleukin-17 Production Through Toll-Like Receptor 3 in Alcohol-associated Liver Injury.Hepatology (Baltimore, Md.) · 2020Article
- Deep proteome profiling reveals novel pathways associated with pro-inflammatory and alcohol-induced microglial activation phenotypes.Journal of proteomics · 2020Article
- Thrombospondin 2/Toll-Like Receptor 4 Axis Contributes to HIF-1α-Derived Glycolysis in Colorectal Cancer.Frontiers in oncology · 2020Article
- Deficient IL-6/Stat3 Signaling, High TLR7, and Type I Interferons in Early Human Alcoholic Liver Disease: A Triad for Liver Damage and Fibrosis.Hepatology communications · 2019Article
- Deep sequencing and miRNA profiles in alcohol-induced neuroinflammation and the TLR4 response in mice cerebral cortex.Scientific reports · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Binge/moderate alcohol suppresses TLR4-MyD88 proinflammatory cytokines; however, alcohol's effects on TLR-TRIF signaling, especially after in vivo exposure in humans, are unclear. We performed a comparative analysis of the TLR4-MyD88, TLR4-TRIF, and TLR3-TRIF pathways in human monocytes following binge alcohol exposure. Mechanistic regulation of TLR-TRIF signaling by binge alcohol was evaluated by analyzing IRF3 and TBK1, upstream regulator protein phosphatase 1 (PP1), and immunoregulatory stress proteins HspA1A and XBP-1 in alcohol-treated human and mouse monocytes/macrophages. Two approaches for alcohol exposure were used: in vivo exposure of primary monocytes in binge alcohol-consuming human volunteers or in vitro exposure of human monocytes/murine macrophages to physiological alcohol concentrations (25-50 mM ethanol), followed by LPS (TLR4) or polyinosinic-polycytidylic acid (TLR3) stimulation ex vivo. In vivo and in vitro binge alcohol exposure significantly inhibited the TLR4-MyD88 cytokines TNF-α and IL-6, as well as the TLR4-TRIF cytokines/chemokines IFN-β, IP-10, and RANTES, in human monocytes, but not TLR3-TRIF-induced cytokines/chemokines, as detected by quantitative PCR and ELISA. Mechanistic analyses revealed TBK-1-independent inhibition of the TLR4-TRIF effector IRF3 in alcohol-treated macrophages. Although stress protein XBP-1, which is known to regulate IRF3-mediated IFN-β induction, was not affected by alcohol, HspA1A was induced by in vivo alcohol in human monocytes. Alcohol-induced HspA1A was required for inhibition of TLR4-MyD88 signaling but not TLR4-TRIF cytokines in macrophages. In contrast, inhibition of PP1 prevented alcohol-mediated TLR4-TRIF tolerance in macrophages. Collectively, our results demonstrate that in vivo and in vitro binge alcohol exposure in humans suppresses TLR4-MyD88 and TLR4-TRIF, but not TLR3-TRIF, responses. Whereas alcohol-mediated effects on the PP1-IRF3 axis inhibit the TLR4-TRIF pathway, HspA1A selectively suppresses the TLR4-MyD88 pathway in monocytes/macrophages.
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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.