ArticleJournal of hepatology2020
Inhibition of IRAK4 kinase activity improves ethanol-induced liver injury in mice.
Article in Journal of hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Screening for medicine and food homologous ingredients targeting ALDH2 to alleviate acute ethanol-induced liver injury.Frontiers in nutrition · 2026Article
- IL-1 family of cytokines in gastrointestinal and liver disorders.Nature reviews. Gastroenterology & hepatology · 2026Review
- Apelin aggravates inflammatory response and hepatic steatosis in alcohol-associated liver disease via ERK signaling pathway.Frontiers in pharmacology · 2026Article
- Identification of CTSK as a TLR-related critical biomarker in liver cirrhosis via integrative bioinformatics and pathological characterization.Scientific reports · 2025Article
- Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer.Acta pharmaceutica Sinica. B · 2024Review
- Mesenchymal stem/stromal cells armored by FGF21 ameliorate alcohol-induced liver injury through modulating polarization of macrophages.Hepatology communications · 2024Article
- Unraveling Extremely DamagingJournal of personalized medicine · 2023Article
- Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.Clinical and experimental medicine · 2023Review
- Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis.Science advances · 2023Article
- Magnetic Fields Affect Alcoholic Liver Disease by Liver Cell Oxidative Stress and Proliferation Regulation.Research (Washington, D.C.) · 2023Article
- Interorgan communication with the liver: novel mechanisms and therapeutic targets.Frontiers in immunology · 2023Review
- Inhibition of IRAK 1/4 alleviates colitis by inhibiting TLR4/ NF-κB pathway and protecting the intestinal barrier.Bosnian journal of basic medical sciences · 2022Article
- The Integrated "Multiomics" Landscape at Peak Injury and Resolution From Alcohol-Associated Liver Disease.Hepatology communications · 2022Article
- A Pan-Cancer Analysis of IRAK1 Expression and Their Association With Immunotherapy Response.Frontiers in molecular biosciences · 2022Article
- Drug Discovery in Liver Disease Using Kinome Profiling.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUNDS &
aimsAlcohol-related liver disease (ALD) is a major cause of chronic liver disease worldwide with limited therapeutic options. Interleukin-1 receptor associated kinase 4 (IRAK4), the master kinase of Toll-like receptor (TLR)/IL-1R-mediated signalling activation, is considered a novel therapeutic target in inflammatory diseases, but has not been investigated in the context of ALD.
methodsIRAK4 phosphorylation and IRAK1 protein were analysed in liver from alcohol-related hepatitis patients and healthy controls. IRAK4 kinase activity-inactive knock-in (Irak4 KI) mice and bone marrow chimeric mice were exposed to chronic ethanol-induced liver injury. IL-1β-induced IRAK4-mediated signalling and acute phase response were investigated in cultured hepatocytes. IRAK1/4 inhibitor was used to test the therapeutic potential for ethanol-induced liver injury in mice.
resultsIncreased IRAK4 phosphorylation and reduced IRAK1 protein were found in livers of patients with alcoholic hepatitis. In the chronic ethanol-induced liver injury mouse model, hepatic inflammation and hepatocellular damage were attenuated in Irak4 KI mice. IRAK4 kinase activity promotes expression of acute phase proteins in response to ethanol exposure, including C-reactive protein and serum amyloid A1 (SAA1). SAA1 and IL-1β synergistically exacerbate ethanol-induced cell death ex vivo. Pharmacological blockage of IRAK4 kinase abrogated ethanol-induced liver injury, inflammation, steatosis, as well as acute phase gene expression and protein production in mice.
conclusionsOur data elucidate the critical role of IRAK4 kinase activity in the pathogenesis of ethanol-induced liver injury in mice and provide preclinical validation for use of an IRAK1/4 inhibitor as a new potential therapeutic strategy for the treatment of ALD. LAY SUMMARY: Herein, we have identified the role of IRAK4 kinase activity in the development of alcohol-induced liver injury in mice. Hepatocyte-specific IRAK4 is associated with an acute phase response and release of proinflammatory cytokines/chemokines, which synergistically exacerbate alcohol-induced hepatocyte cell death ex vivo. Pharmacological inhibition of IRAK4 kinase activity effectively attenuates alcohol-induced liver injury in mice and could have therapeutic implications.
Indexed as
Identifiers
What OpenQuestion holds
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.