ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Moderate alcohol induces stress proteins HSF1 and hsp70 and inhibits proinflammatory cytokines resulting in endotoxin tolerance.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 81 citations in OpenAlex.
- Inflammatory endotoxin challenge in individuals with alcohol use disorder and controls.Alcohol, clinical & experimental research · 2025Trial
- Comorbidities and Inflammation: How Chronic Diseases Prime the Host Response in Sepsis.International journal of molecular sciences · 2026Review
- Serum GRP78 as a potential biomarker for early liver injury and active fibrogenesis in alcohol-associated liver disease.Clinical and experimental medicine · 2026Article
- Heat shock proteins in farmed aquatic animals: advancing animal health and welfare management through building resilience.Frontiers in immunology · 2026Review
- miRNA Expression Profile in Whole Blood of Healthy Volunteers and Moderate Beer Consumption with Meals.Nutrients · 2026Article
- Celastrol Activates HSF1 to Enhance Regulatory T Cells Function and Ameliorate Intestinal Inflammation.Biomolecules · 2025Article
- Alcohol-induced susceptibility to pulmonary bacterial infections: A narrative review.Alcohol, clinical & experimental research · 2025Review
- Targeted Regulation of HSP70 by the ARP2/3 Complex in Mammary Epithelial Cells and Its Impact on Host Cell Apoptosis.Biomolecules · 2025Article
- Effects of moderate beer consumption on immunity and the gut microbiome in immunosuppressed mice.Bioscience of microbiota, food and health · 2025Article
- Adolescent intermittent ethanol (AIE) sensitized fever in male Sprague Dawley rats exposed to poly I:C in adulthood.Brain, behavior, and immunity · 2024Article
- Linking alcohol use to Alzheimer's disease: Interactions with aging and APOE along immune pathways.Medical research archives · 2024Article
- NLRP3 Inflammasome in Acute and Chronic Liver Diseases.International journal of molecular sciences · 2024Review
- Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity.Pharmaceuticals (Basel, Switzerland) · 2023Article
- A critical review of recent knowledge of alcohol's effects on the immunological response in different tissues.Alcohol, clinical & experimental research · 2023Review
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- The Correlation between Extracellular Heat Shock Protein 70 and Lipid Metabolism in a Ruminant Model.Metabolites · 2021Article
- Moderate Beer Intake Downregulates Inflammasome Pathway Gene Expression in Human Macrophages.Biology · 2021Article
- HSF1 is involved in suppressing A1 phenotype conversion of astrocytes following spinal cord injury in rats.Journal of neuroinflammation · 2021Article
- Ethanol: striking the cardiovascular system by harming the gut microbiota.American journal of physiology. Heart and circulatory physiology · 2021Review
- Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway.Molecular medicine (Cambridge, Mass.) · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Binge or moderate alcohol exposure impairs host defense and increases susceptibility to infection because of compromised innate immune responses. However, there is a lack of consensus on the molecular mechanism by which alcohol mediates this immunosuppression. In this study, we show that cellular stress proteins HSF1 and hsp70 play a mechanistic role in alcohol-mediated inhibition of the TLR4/MyD88 pathway. Alcohol exposure induced transcription factor HSF1 mRNA expression and DNA binding activity in primary human monocytes and murine macrophages. Furthermore, HSF1 target gene hsp70 mRNA and protein are upregulated by alcohol in monocytes. In vitro pre-exposure to moderate alcohol reduced subsequent LPS-induced NF-κB promoter activity and downstream TNF-α, IL-6 and IL-1β production in monocytes and macrophages, exhibiting endotoxin tolerance. Mechanistic analysis demonstrates that alcohol-induced HSF1 binds to the TNF-α promoter in macrophages at early time points, exerting transrepression and decreased TNF-α expression. Furthermore, association of hsp70 with NF-κB subunit p50 in alcohol-treated macrophages correlates with reduced NF-κB activation at later time points. Hsp70 overexpression in macrophages was sufficient to block LPS-induced NF-κB promoter activity, suggesting alcohol-mediated immunosuppression by hsp70. The direct crosstalk of hsp70 and HSF1 was further confirmed by the loss of alcohol-mediated endotoxin tolerance in hsp70- and HSF1-silenced macrophages. Our data suggest that alcohol-mediated activation of HSF1 and induction of hsp70 inhibit TLR4-MyD88 signaling and are required for alcohol-induced endotoxin tolerance. Using stress proteins as direct drug targets would be clinically relevant in alcohol abuse treatment and may serve to provide a better understanding of alcohol-mediated immunosuppression.
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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.