ArticleMucosal immunology2019
Alcohol-induced IL-17A production in Paneth cells amplifies endoplasmic reticulum stress, apoptosis, and inflammasome-IL-18 activation in the proximal small intestine in mice.
Article in Mucosal immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Influence of Alcohol on the Intestinal Immune System.Alcohol research : current reviews · 2025Pooled it
- The "Immune Rebellion" from the Intestines to the Liver: A Vicious Cycle That Causes the Liver to Collapse.Metabolites · 2026Review
- Effect of 1-DNJ on Oxidative Stress-Induced Apoptosis in Porcine Ovarian GCs Through Modulation of the PERK-ATF4/MFN2 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Prodelphinidin from purple sweet potato induces apoptosis in human triple-negative breast cancer cells via ROS-mediated ER stress activation.Medical oncology (Northwood, London, England) · 2025Article
- Luteolin attenuates LPS-induced damage in IPEC-J2 cells by enhancing mitophagy via AMPK signaling pathway activation.Frontiers in nutrition · 2025Article
- Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease.Hepatology (Baltimore, Md.) · 2024Review
- Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease.eGastroenterology · 2024Article
- Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.Clinical and molecular hepatology · 2024Review
- Heat stress induces calcium dyshomeostasis to subsequent cognitive impairment through ERS-mediated apoptosis via SERCA/PERK/eIF2α pathway.Cell death discovery · 2024Article
- Spatial Proteomics Reveals Alcohol-Induced Damages to the Crypts and Villi of the Mouse Small Intestine.Journal of proteome research · 2024Article
- The Dynamic Role of Endoplasmic Reticulum Stress in Chronic Liver Disease.The American journal of pathology · 2023Review
- Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn's disease.iScience · 2023Article
- Paneth cells as the cornerstones of intestinal and organismal health: a primer.EMBO molecular medicine · 2023Review
- Paneth cell development in the neonatal gut: pathway regulation, development, and relevance to necrotizing enterocolitis.Frontiers in cell and developmental biology · 2023Review
- Multifaceted involvements of Paneth cells in various diseases within intestine and systemically.Frontiers in immunology · 2023Review
- Therapeutic Perspectives of IL1 Family Members in Liver Diseases: An Update.Journal of clinical and translational hepatology · 2022Review
- Effects of the Gut Microbiota and Barrier Function on Melatonin Efficacy in Alleviating Liver Injury.Antioxidants (Basel, Switzerland) · 2022Article
- Trehalose Attenuates Oxidative Stress and Endoplasmic Reticulum Stress-Mediated Apoptosis in IPEC-J2 Cells Subjected to Heat Stress.Animals : an open access journal from MDPI · 2022Article
- Article
- CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) Deficiency Attenuates Heatstroke-Induced Intestinal Injury.Inflammation · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Gut microbial translocation contributes to alcoholic hepatitis. Using a mouse model of alcoholic hepatitis, we investigated the effects of chronic alcohol plus binge and found increased abundance of Paneth cells and IL-17A in the proximal small intestine (PSI). Alcohol increased IL-17A production and pro-apoptotic signaling evidenced by Bax, Bim, caspase-3, and caspase-8 increases via endoplasmic reticulum (ER) stress indicated by C/EBP homologous protein (CHOP) upregulation; this was prevented by the ER stress inhibitor, 4-PBA, in isolated crypts in vitro and in vivo. Mechanistically, IL-17 augmented alcohol-induced ER stress in isolated crypts. In vivo IL-17A blocking antibody administration in alcohol-treated mice attenuated ER stress-mediated apoptosis and IL-18 induction and prevented alcohol-induced impairment of tight junctions in the PSI and LPS translocation to the liver. Acute-on-chronic alcohol resulted in inflammasome activation, caspase-1 cleavage, and IL-18 production in the PSI. In vivo treatment with antibiotics or 4-PBA prevented CHOP upregulation and inflammasome activation. Our data suggest that alcohol upregulates innate immune mechanisms by increasing Paneth cell numbers and IL-17A release contributing to apoptosis amplification, inflammasome activation, and gut leakiness in the PSI. Binge alcohol-induced Paneth cell expansion, ER stress, and inflammasome activation in the PSI are modulated by the gut microbiome.
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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.