ArticleHepatology (Baltimore, Md.)2017
Hepatic mitochondrial DNA/Toll-like receptor 9/MicroRNA-223 forms a negative feedback loop to limit neutrophil overactivation and acetaminophen hepatotoxicity in mice.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- The use of circulating miRNAs for the diagnosis, prognosis, and personalized treatment of MASLD.Journal of physiology and biochemistry · 2025Pooled it
- The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy.International journal of molecular sciences · 2022Pooled it
- TLR9-mediated innate immune signaling contributes to acetaminophen-induced injury in the developing lung.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- miR-375 protects against acetaminophen-induced acute liver failure by orchestrating pharmacogene expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Palmitic acid reduces LDLR-dependent uptake of macrophage-derived extracellular vesicles by hepatoma cells.Non-coding RNA research · 2025Article
- Synergistic effects of NF-κB1 and inflammatory pathway polymorphisms on hypertension and dyslipidemia susceptibility in type 2 diabetes.Diabetology & metabolic syndrome · 2025Article
- Temporal dichotomy of neutrophil function in acute liver injury and repair.JHEP reports : innovation in hepatology · 2025Article
- miR-324-3p Suppresses Hepatic Stellate Cell Activation and Hepatic Fibrosis Via Regulating SMAD4 Signaling Pathway.Molecular biotechnology · 2025Article
- Neutrophil Recruitment via Hepatocyte IL-1α Drives NETs-Mediated AIM2 Hepatocyte Apoptosis in Alcohol-associated steatohepatitis.International journal of biological sciences · 2025Article
- The value of fibroblast growth factor 21 (FGF21) promoter methylation in the repair and regeneration during the course of chronic hepatitis B.Frontiers in cell and developmental biology · 2025Article
- Molecular dynamics of inflammation resolution: therapeutic implications.Frontiers in cell and developmental biology · 2025Review
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- Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.Acta pharmacologica Sinica · 2024Article
- Role of immune cell interactions in alcohol-associated liver diseases.Liver research (Beijing, China) · 2024Review
- [Study based on the acetaldehyde dehydrogenase 2 gene polymorphism and acetaminophen-induced liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Biomarkers of Hepatic Toxicity: An Overview.Current therapeutic research, clinical and experimental · 2024Review
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- Allii Macrostemonis Bulbus: A Comprehensive Review of Ethnopharmacology, Phytochemistry and Pharmacology.Molecules (Basel, Switzerland) · 2023Review
- Mitophagy-promoting miR-138-5p promoter demethylation inhibits pyroptosis in sepsis-associated acute lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Acetaminophen (APAP) overdose is a leading cause of acute liver failure worldwide, in which mitochondrial DNA (mtDNA) released by damaged hepatocytes activates neutrophils through binding of Toll-like receptor 9 (TLR9), further aggravating liver injury. Here, we demonstrated that mtDNA/TLR9 also activates a negative feedback pathway through induction of microRNA-223 (miR-223) to limit neutrophil overactivation and liver injury. After injection of APAP in mice, levels of miR-223, the most abundant miRNAs in neutrophils, were highly elevated in neutrophils. Disruption of the miR-223 gene exacerbated APAP-induced hepatic neutrophil infiltration, oxidative stress, and injury and enhanced TLR9 ligand-mediated activation of proinflammatory mediators in neutrophils. An additional deletion of the intercellular adhesion molecule 1 (ICAM-1) gene ameliorated APAP-induced neutrophil infiltration and liver injury in miR-223 knockout mice. In vitro experiments revealed that miR-223-deficient neutrophils were more susceptible to TLR9 agonist-mediated induction of proinflammatory mediators and nuclear factor kappa B (NF-κB) signaling, whereas overexpression of miR-223 attenuated these effects in neutrophils. Moreover, inhibition of TLR9 signaling by either treatment with a TLR9 inhibitor or by disruption of TLR9 gene partially, but significantly, suppressed miR-223 expression in neutrophils post-APAP injection. In contrast, activation of TLR9 up-regulated miR-223 expression in neutrophils in vivo and in vitro. Mechanistically, activation of TLR9 up-regulated miR-223 by enhancing NF-κB binding on miR-223 promoter, whereas miR-223 attenuated TLR9/NF-κB-mediated inflammation by targeting IκB kinase α expression. Collectively, up-regulation of miR-223 plays a key role in terminating the acute neutrophilic response and is a therapeutic target for treatment of APAP-induced liver failure. (Hepatology 2017;66:220-234).
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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.