ArticleGut2024
Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis.
Article in Gut, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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
56 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Neutrophil extracellular traps (NETs) and NETosis in alcohol-associated diseases: A systematic review.Alcohol, clinical & experimental research · 2025Pooled it
- From mechanisms to anti-fibrotic drugs in hepatic stellate cell research: a global bibliometric analysis with patent and clinical perspectives (2000-2025).Frontiers in pharmacology · 2025Pooled it
- siRNA therapeutics for metabolic dysfunction-associated Steatohepatitis: Targets, delivery, clinical evidence, and translational challenges.Biochemistry and biophysics reports · 2026Review
- Metabolic dysfunction-associated steatotic liver disease: pathogenic mechanisms and exercise-induced molecular adaptations.Lipids in health and disease · 2026Review
- VISTA+ Neutrophils Contribute to Platinum Resistance by Suppressing CD8+ T Cells in High-Grade Serous Ovarian Cancer.Cancer immunology research · 2026Article
- Uncovering immune dysfunction in ACLF: Cellular mechanisms, molecular pathways, and therapeutic frontiers.Journal of hepatology · 2026Review
- Neutrophil depletion exacerbatesFood and waterborne parasitology · 2026Article
- Review
- The emerging role of neutrophil extracellular traps in liver diseases: a narrative review.Medical molecular morphology · 2026Review
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
- EGFR orchestrates neutrophil activation and NETosis via CEBPβ-dependent PGLYRP1 induction.Cell death and differentiation · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- IL-17B protects against uropathogenicMicrobiology spectrum · 2026Article
- NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Metabolic dysfunction-associated steatotic liver disease: pathogenesis and novel treatment options.Molecular biomedicine · 2026Review
- Multiomic insights into the MPO-mediated NET formation pathway in alcohol-induced epilepsy risk.Genes & diseases · 2026Article
- A preliminary study on NLRP3 activation and the interventional effects of MCC950 in Con A-induced EAH mice.Translational pediatrics · 2026Article
- Magnesium-tannic acid nanomedicines reprogram pro-fibrotic macrophages for hepatic fibrosis treatment via restoring endoplasmic reticulum homeostasis.Journal of nanobiotechnology · 2026Article
- Article
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.
Funding
Abstract
objectiveAlcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH.
designC57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges. Neutrophil infiltration, neutrophil extracellular traps (NETs) and fibrosis were evaluated.
resultsWe found that alcohol binges in MASH increase liver injury and fibrosis. Liver transcriptomic profiling revealed differential expression of genes involved in extracellular matrix reorganisation, neutrophil activation and inflammation compared with alcohol or the MASH diet alone. Alcohol binges specifically increased NET formation in MASH livers in mice, and NETs were also increased in human livers with MASH plus alcohol use. We discovered that cell-free NETs are sensed via Nod-like receptor protein 3 (NLRP3). Furthermore, we show that cell-free NETs in vitro induce a profibrotic phenotype in hepatic stellate cells (HSCs) and proinflammatory monocytes. In vivo, neutrophil depletion using anti-Ly6G antibody or NET disruption with deoxyribonuclease treatment abrogated monocyte and HSC activation and ameliorated liver damage and fibrosis. In vivo, inhibition of NLRP3 using MCC950 or NLRP3 deficiency attenuated NET formation, liver injury and fibrosis in MASH plus alcohol diet-fed mice (graphical abstract).
conclusionAlcohol binges promote liver fibrosis via NET-induced activation of HSCs and monocytes in MASH. Our study highlights the potential of inhibition of NETs and/or NLRP3, as novel therapeutic strategies to combat the profibrotic effects of alcohol in MASH.
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.