ArticleAlcoholism, clinical and experimental research2020
Inhibition of HSP90 and Activation of HSF1 Diminish Macrophage NLRP3 Inflammasome Activity in Alcohol-Associated Liver Injury.
Article in Alcoholism, clinical and experimental research, 2020. 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, 60 citations in OpenAlex.
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- Plasma proteomic profiling of septic shock and acute pancreatitis identifies shared signatures and disease-specific pathways.Scientific reports · 2026Article
- Amygdalin synergizes with the TNF-α monoclonal antibody infliximab to modulate HSP90 and related necro-inflammatory/oxidative stress pathways in a rat model of hepatic I/R.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mechanism Study on the Regulation of Intestinal Microecology by Hangover Liver-Protecting Beverage for the Treatment of Alcoholic Liver Disease.Food science & nutrition · 2026Article
- Astragalus Polysaccharide Nanoparticles Alleviate Sepsis-Induced Myocardial Injury by Targeting the HSP90AA1/NLRP3 Signaling Pathway.International journal of nanomedicine · 2026Article
- Identification of Wnt/β-catenin- and immune-related genes in hepatic ischemia-reperfusion injury using bulk transcriptomics, single-cell RNA sequencing, and a murine model.Frontiers in immunology · 2026Article
- Integrated network pharmacology and molecular docking reveal multi-target hepatotoxic mechanisms of Xanthii fructus.Medicine · 2025Article
- Cancer suppresses mitochondrial chaperone activity in macrophages to drive immune evasion.Nature immunology · 2025Article
- HSPA1A Can Alleviate CFA-Induced Inflammatory Pain by Modulating Macrophages.International journal of molecular sciences · 2025Article
- Role of HSP90 in Type 2 Diabetes Mellitus and Its Association with Liver Diseases.Molecular biotechnology · 2025Review
- Hsp90 inhibition attenuates the 1, 2-Dichloroethane-induced cognitive impairment by blocking NLRP3 inflammasome activation in mice.Toxicology research · 2025Article
- Investigation of Potential Targets for Bupleuri Radix in the Treatment of Subacute Thyroiditis.International journal of endocrinology · 2025Article
- Upregulation of HSP90α in the lungs and circulation in sarcoidosis.Frontiers in medicine · 2025Article
- Rab11b promotes M1-like macrophage polarization by restraining autophagic degradation of NLRP3 in alcohol-associated liver disease.Acta pharmacologica Sinica · 2025Article
- A computational framework to in silico screen for drug-induced hepatocellular toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Intestinal microbiota homeostasis analysis in riboflavin-treated alcoholic liver disease.Communications biology · 2024Article
- The Role of Alarmins in the Pathogenesis of Atherosclerosis and Myocardial Infarction.Current issues in molecular biology · 2024Review
- Effect of ethanol exposure on innate immune response in sepsis.Journal of leukocyte biology · 2024Review
- NLRP3 Inflammasome in Acute and Chronic Liver Diseases.International journal of molecular sciences · 2024Review
- Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol-Liver-Intestine Axis Health.International journal of molecular sciences · 2024Review
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8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundActivation of NLRP3 in liver macrophages contributes to alcohol-associated liver disease (ALD). Molecular chaperone heat shock protein (HSP) 90 facilitates NLRP3 inflammasome activity during infections and inflammatory diseases. We previously reported that HSP90 is induced in ALD and regulates proinflammatory cytokines, tumor necrosis factor alpha, and IL-6. Whether HSP90 affects IL-1β and IL-18 regulated by NLRP3 inflammasome in ALD is unknown. Here, we hypothesize that HSP90 modulated NLRP3 inflammasome activity and affects IL-1β and IL-18 secretion in ALD.
methodsThe expression of HSP90AA1 and NLRP3 inflammasome genes was evaluated in human alcoholic livers and in mouse model of ALD. The importance of HSP90 on NLRP3 inflammasome activation in ALD was evaluated by administering HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) to mice subjected to ALD, and in vitro to bone marrow-derived macrophages (BMDM) stimulated with LPS and ATP. The effect of activation of HSF1/HSPA1A axis during HSP90 inhibition or direct activation during heat shock of BMDMs on NLRP3 activity and secretion of downstream cytokines was evaluated.
resultsWe found positive correlation between induction of HSP90 and NLRP3 inflammasome genes in human alcoholic cirrhotic livers. Administration of 17-DMAG in mouse model of ALD significantly down-regulated NLRP3 inflammasome-mediated caspase-1 (CASP-1) activity and cytokine secretion, with reduction in ALD. 17-DMAG-mediated decrease in NLRP3 was restricted to liver macrophages. Using BMDMs, we show that inhibition of HSP90 prevented CASP-1 activity, and Gasdermin D (GSDMD) cleavage, important in release of active IL-1β and IL-18. Interestingly, activation of the heat shock factor 1 (HSF1)/HSPA1A axis, either during HSP90 inhibition or by heat shock, decreased NLRP3 inflammasome activity and reduced secretion of cytokines.
conclusionOur studies indicate that inhibition of HSP90 and activation of HSF1/HSPA1A reduce IL-1β and IL-18 via decrease in NLRP3/CASP-1 and GSDMD activity in ALD.
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