ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Histones activate the NLRP3 inflammasome in Kupffer cells during sterile inflammatory liver injury.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 216 citations in OpenAlex.
- Integrated single-cell multiomics reveals neutrophil-driven immune-metabolic reprogramming of Kupffer cells via thrombospondin-1/CD36 after surgical stress.JCI insight · 2026Article
- Dual Targeting of Net Formation and Coagulation Improves Survival and Organ Protection in Experimental Sepsis.Shock (Augusta, Ga.) · 2026Article
- Association of Pro-Inflammatory Diets With Increased Risk of Metabolic Dysfunction-Associated Steatohepatitis: Evidence From a Prospective Cohort Study.Food science & nutrition · 2026Article
- The Liver-Testis Axis: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2026Review
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- All-in-one: a CGRP-encapsulated Rh-GelMA supramolecular dual-network hydrogel orchestrating immune-vascular coupling for diabetic wound healing.Journal of nanobiotechnology · 2026Article
- Hepatocyte-Derived Apoptotic Bodies as Pathological Intercellular Messengers in the Liver.Biomolecules · 2026Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Damage-associated molecular patterns in hepatic ischemia-reperfusion injury: spatiotemporal signatures, biomarker potential, and clinical translation.Frontiers in immunology · 2026Review
- Research Trends in Neutrophil Extracellular Traps and Ischemia-Reperfusion Injury: A Dual-Database Bibliometric Analysis from 2013 to 2025.Journal of inflammation research · 2026Article
- NLRP3/Caspase-1 Regulate Macrophage Efferocytosis by Modulating ADAM17-Mediated MerTK Cleavage in Liver Ischemia-Reperfusion Injury.Research (Washington, D.C.) · 2026Article
- Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention.World journal of experimental medicine · 2025Review
- Sepsis and the Liver.Diseases (Basel, Switzerland) · 2025Review
- Aprepitant alleviates acute lung injury in a rat model of hepatic ischemia-reperfusion via NLRP3/IL-1β signaling pathway.Scientific reports · 2025Article
- Histones present on the surface of late apoptotic cells induce RAGE-mediated phagocytosis.Cell communication and signaling : CCS · 2025Article
- Innate Immune Surveillance and Recognition of Epigenetic Marks.Epigenomes · 2025Review
- Damage-associated molecular patterns (DAMPs) in diseases: implications for therapy.Molecular biomedicine · 2025Review
- Article
- Mechanism of action of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome and its regulation in liver injury.Chinese medical journal · 2025Review
- "The NET effect": Neutrophil extracellular traps-a potential key component of the dysregulated host immune response in sepsis.Critical care (London, England) · 2025Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Cellular processes that drive sterile inflammatory injury after hepatic ischemia/reperfusion (I/R) injury are not completely understood. Activation of the inflammasome plays a key role in response to invading intracellular pathogens, but mounting evidence suggests that it also plays a role in inflammation driven by endogenous danger-associate molecular pattern molecules released after ischemic injury. The nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) inflammasome is one such process, and the mechanism by which its activation results in damage and inflammatory responses following liver I/R is unknown. In this article, we report that both NLRP3 and its downstream target caspase-1 are activated during I/R and are essential for hepatic I/R injury, because both NLRP3 and caspase-1 knockout mice are protected from injury. Furthermore, inflammasome-mediated injury is dependent on caspase-1 expression in liver nonparenchymal cells. Although upstream signals that activate the inflammasome during ischemic injury are not well characterized, we show that endogenous extracellular histones activate the NLRP3 inflammasome during liver I/R through TLR9. This occurs through TLR9-dependent generation of reactive oxygen species. This mechanism is operant in resident liver Kupffer cells, which drive innate immune responses after I/R injury by recruiting additional cell types, including neutrophils and inflammatory monocytes. These novel findings illustrate a new mechanism by which extracellular histones and activation of NLRP3 inflammasome contribute to liver damage and the activation of innate immunity during sterile inflammation.
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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.