ArticlePloS one2014
Release of neuronal HMGB1 by ethanol through decreased HDAC activity activates brain neuroimmune signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 166 citations in OpenAlex.
- Integrated Network and Transcriptomic Analyses Identify a Candidate Ethanol-ADAM17 Molecular Axis Associated with Glioblastoma Progression.International journal of molecular sciences · 2026Article
- Epigenetic Repression of the Serotonergic Neuron Phenotype Following Adolescent Binge Drinking Is Restored through Inhibition of Proinflammatory Signaling by Exercise and Glycyrrhizic Acid.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- HMGB1-mediated enhancement of glycolysis activates hepatic stellate cells by inhibiting ferroptosis in alcoholic hepatic fibrosis.Stem cell research & therapy · 2026Article
- Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol.The American journal of pathology · 2026Article
- Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.Molecular medicine (Cambridge, Mass.) · 2025Article
- Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from binge alcohol.bioRxiv : the preprint server for biology · 2025Article
- HMGB1 as an emerging key modulator of bone remodeling: a narrative review.Stem cell research & therapy · 2025Review
- Thiamine Deficiency and Neuroinflammation Are Important Contributors to Alcohol Use Disorder.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Review
- Interleukin-33 Knockout Promotes High Mobility Group Box 1 Release from Astrocytes by Acetylation Mediated by P300/CBP-Associated Factor in Experimental Autoimmune Encephalomyelitis.Neuroscience bulletin · 2025Article
- Suppression of NF-κB/NLRP3 by nanoligomer therapy mitigates ethanol and advanced age-related neuroinflammation.Journal of leukocyte biology · 2025Article
- Involvement of circadian clock protein PER2 in controlling sleep deprivation induced HMGB1 up-regulation by targeting p300 in the cortex.Scientific reports · 2025Article
- Ethanol-induced changes in neurotrophic and immune genes are regulated by receptor-type protein tyrosine phosphatase β/ζ (RPTPβ/ζ) and microglial-neuronal interactions.Frontiers in genetics · 2025Article
- Impact of Neuroimmune System Activation by Adolescent Binge Alcohol Exposure on Adult Neurobiology.Advances in experimental medicine and biology · 2025Review
- Biophysically stressed vascular smooth muscle cells express MCP-1The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Effect of ethanol exposure on innate immune response in sepsis.Journal of leukocyte biology · 2024Review
- Binge ethanol exposure in advanced age elevates neuroinflammation and early indicators of neurodegeneration and cognitive impairment in female mice.Brain, behavior, and immunity · 2024Article
- Post-translational modifications in sepsis-induced organ dysfunction: mechanisms and implications.Frontiers in immunology · 2024Review
- Alcohol, HMGB1, and Innate Immune Signaling in the Brain.Alcohol research : current reviews · 2024Review
- The involvement of HDAC3 in the pathogenesis of lung injury and pulmonary fibrosis.Frontiers in immunology · 2024Review
- Epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol (AIE) exposure and in human AUD.Advances in drug and alcohol research · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Neuroimmune gene induction is involved in many brain pathologies including addiction. Although increased expression of proinflammatory cytokines has been found in ethanol-treated mouse brain and rat brain slice cultures as well as in post-mortem human alcoholic brain, the mechanisms remain elusive. High-mobility group box 1 (HMGB1) protein is a nuclear protein that has endogenous cytokine-like activity. We previously found increased HMGB1 in post-mortem alcoholic human brain as well as in ethanol treated mice and rat brain slice cultures. The present study investigated the mechanisms for ethanol-induced release of HMGB1 and neuroimmune activation in a model of rat hippocampal-entorhinal cortex (HEC) brain slice cultures. Ethanol exposure triggered dose-dependent HMGB1 release, predominantly from neuronal cells. Inhibitors of histone deacetylases (HDACs) promoted nucleocytoplasmic mobilization of HDAC1/4 and HMGB1 resulting in increased total HMGB1 and acetylated HMGB1 release. Similarly, ethanol treatment was found to induce the translocation of HDAC1/4 and HMGB1 proteins from nuclear to cytosolic fractions. Furthermore, ethanol treatment reduced HDAC1/4 mRNA and increased acetylated HMGB1 release into the media. These results suggest decreased HDAC activity may be critical in regulating acetylated HMGB1 release from neurons in response to ethanol. Ethanol and HMGB1 treatment increased mRNA expression of proinflammatory cytokines TNFα and IL-1β as well as toll-like receptor 4 (TLR4). Targeting HMGB1 or microglial TLR4 by using siRNAs to HMGB1 and TLR4, HMGB1 neutralizing antibody, HMGB1 inhibitor glycyrrhizin and TLR4 antagonist as well as inhibitor of microglial activation all blocked ethanol-induced expression of proinflammatory cytokines TNFα and IL-1β. These results support the hypothesis that ethanol alters HDACs that regulate HMGB1 release and that danger signal HMGB1 as endogenous ligand for TLR4 mediates ethanol-induced brain neuroimmune signaling through activation of microglial TLR4. These findings provide new therapeutic targets for brain neuroimmune activation and alcoholism.
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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.