ArticleJournal of hepatology2015
Inhibition of sterile danger signals, uric acid and ATP, prevents inflammasome activation and protects from alcoholic steatohepatitis in mice.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
What it found
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Who cites it
83 citing papers in PubMed, 136 citations in OpenAlex.
- Early urate-lowering therapy in gouty arthritis with acute flares: a double-blind placebo controlled clinical trial.European journal of medical research · 2023Trial
- Liver Fibrosis and Purinergic Signaling: Autocrine-Paracrine Role of ATP in Liver Damage.International journal of molecular sciences · 2026Review
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- IL-1 family of cytokines in gastrointestinal and liver disorders.Nature reviews. Gastroenterology & hepatology · 2026Review
- Purinergic signaling in liver disease: calcium signaling and induction of inflammation.Purinergic signalling · 2025Review
- Neutrophil Recruitment via Hepatocyte IL-1α Drives NETs-Mediated AIM2 Hepatocyte Apoptosis in Alcohol-associated steatohepatitis.International journal of biological sciences · 2025Article
- NLRP3 Inflammasome Activation in Liver Disorders: From Molecular Pathways to Therapeutic Strategies.Journal of inflammation research · 2025Review
- Association between Hp infection and serum uric acid to high-density lipoprotein cholesterol ratio in adults.Frontiers in medicine · 2025Article
- Eprosartan Reduces Inflammation and Oxidative Stress in Ethanol-induced Hepatotoxicity.Current pharmaceutical design · 2025Article
- Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2024Review
- 3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation.The EPMA journal · 2024Article
- Endothelial Dysfunction and Liver Cirrhosis: Unraveling of a Complex Relationship.International journal of molecular sciences · 2024Review
- Inflammasomes in chronic liver disease: Hepatic injury, fibrosis progression and systemic inflammation.Journal of hepatology · 2024Review
- Article
- Endogenous ethanol production in health and disease.Nature reviews. Gastroenterology & hepatology · 2024Review
- Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease.Scientific reports · 2024Article
- LanGui tea, an herbal medicine formula, protects against binge alcohol-induced acute liver injury by activating AMPK-NLRP3 signaling.Chinese medicine · 2024Article
- Cell Death in Liver Disease and Liver Surgery.Biomedicines · 2024Review
- The role of inflammasomes in human diseases and their potential as therapeutic targets.Signal transduction and targeted therapy · 2024Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe inflammasome is a well-characterized inducer of inflammation in alcoholic steatohepatitis (ASH). Inflammasome activation requires two signals for mature interleukin (IL)-1β production. Here we asked whether metabolic danger signals trigger inflammasome activation in ASH.
methodsWild-type mice, ATP receptor 2x7 (P2rx7)-KO mice, or mice overexpressing uricase were fed Lieber-DeCarli ethanol or control diet. We also implemented a pharmacological approach in which mice were treated with probenecid or allopurinol.
resultsThe sterile danger signals, ATP and uric acid, were increased in the serum and liver of alcohol-fed mice. Depletion of uric acid or ATP, or lack of ATP signaling attenuated ASH and prevented inflammasome activation and its major downstream cytokine, IL-1β. Pharmacological depletion of uric acid with allopurinol provided significant protection from alcohol-induced inflammatory response, steatosis and liver damage, and additional protection was achieved in mice treated with probenecid, which depletes uric acid and blocks ATP-induced P2rx7 signaling. We found that alcohol-damaged hepatocytes released uric acid and ATP in vivo and in vitro and that these sterile danger signals activated the inflammasome in LPS-exposed liver mononuclear cells.
conclusionsOur data indicate that the second signal in inflammasome activation and IL-1β production in ASH results from the endogenous danger signals, uric acid and ATP. Inhibition of signaling triggered by uric acid and ATP may have therapeutic implications in ASH.
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