ArticleGut2017
Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors.
Article in Gut, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- [Alcohol liver disease: immunoregulatory mechanisms and precision therapeutic targets].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Integration of Transcriptomics and Mammary Epithelial Cell Models Reveals the Regulatory Mechanism of CXCR1 in E. Coli-Induced Bovine Mastitis.Applied biochemistry and biotechnology · 2026Article
- Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease.Cellular & molecular immunology · 2025Review
- New therapeutic target for alcohol-associated hepatitis (AH): AH-associated IL-8eGastroenterology · 2024Article
- Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Role of Cytokines in the Pathogenesis and Treatment of Alcoholic Liver Disease.Diseases (Basel, Switzerland) · 2024Review
- Alcohol-associated liver disease.The Journal of clinical investigation · 2024Review
- ADRB2 serves as a novel biomarker and attenuates alcoholic hepatitis via the SIRT1/PGC-1α/PPARα pathway: integration of WGCNA, machine learning and experimental validation.Frontiers in pharmacology · 2024Article
- Multifunctional roles of inflammation and its causative factors in primary liver cancer: A literature review.World journal of hepatology · 2023Review
- Gastric cancer mesenchymal stem cells via the CXCR2/HK2/PD-L1 pathway mediate immunosuppression.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Therapeutic inhibition of CXCR1/2: where do we stand?Internal and emergency medicine · 2023Review
- Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease.International journal of molecular sciences · 2023Review
- Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.Annual review of pathology · 2023Review
- The immunological function of CXCR2 in the liver during sepsis.Journal of inflammation (London, England) · 2022Review
- Alcohol-Related Liver Disease: An Overview on Pathophysiology, Diagnosis and Therapeutic Perspectives.Biomedicines · 2022Review
- Ethanol promoting the upregulation of C-X-C Motif Chemokine Ligand 1（CXCL1） and C-X-C Motif Chemokine Ligand 6（CXCL6） in models of early alcoholic liver disease.Bioengineered · 2022Article
- Immune cells in alcohol-related liver disease.Liver research (Beijing, China) · 2022Review
- Lipopeptide Pepducins as Therapeutic Agents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.Hepatology (Baltimore, Md.) · 2021Article
- Regulation and functional roles of chemokines in liver diseases.Nature reviews. Gastroenterology & hepatology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveAlcoholic steatohepatitis is a life-threatening condition with short-term mortality up to 40%. It features hepatic neutrophil infiltration and blood neutrophilia, and may evolve from ethanol-induced breakdown of the enteric barrier and consequent bacteraemia. Signalling through CXCR1/2 G-protein-coupled-receptors (GPCRs), the interleukin (IL)-8 receptors, is critical for the recruitment and activation of neutrophils. We have developed short lipopeptides (pepducins), which inhibit post-ligand GPCR activation precisely targeting individual GPCRs.
designExperimental alcoholic liver disease was induced by administering alcohol and a Lieber-DeCarli high-fat diet. CXCR1/2 GPCRs were blocked via pepducins either from onset of the experiment or after disease was fully established. Hepatic inflammatory infiltration, hepatocyte lipid accumulation and overall survival were assessed as primary outcome parameters. Neutrophil activation was assessed by myeloperoxidase activity and liver cell damage by aspartate aminotransferase and alanine aminotransferase plasma levels. Chemotaxis assays were performed to identify chemoattractant signals derived from alcohol-exposed hepatocytes.
resultsHere, we show that experimental alcoholic liver disease is driven by CXCR1/2-dependent activation of neutrophils. CXCR1/2-specific pepducins not only protected mice from liver inflammation, weight loss and mortality associated with experimental alcoholic liver disease, but therapeutic administration cured disease and prevented further mortality in fully established disease. Hepatic neutrophil infiltration and triglyceride accumulation was abrogated by CXCR1/2 blockade. Moreover, CXCL-1 plasma levels were decreased with the pepducin therapy as was the transcription of hepatic IL-1β mRNA.
conclusionsWe propose that high circulating IL-8 in human alcoholic hepatitis may cause pathogenic overzealous neutrophil activation, and therapeutic blockade via pepducins merits clinical study.
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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.