ArticlePloS one2013
Toll like receptor 3 plays a critical role in the progression and severity of acetaminophen-induced hepatotoxicity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Generation of pro-and anti-inflammatory mediators after acetaminophen overdose in surviving and non-surviving patients.Toxicology letters · 2022Article
- Genetic and pharmacological inhibition of XBP1 protects against APAP hepatotoxicity through the activation of autophagy.Cell death & disease · 2022Article
- 3'mRNA sequencing reveals pro-regenerative properties of c5ar1 during resolution of murine acetaminophen-induced liver injury.NPJ Regenerative medicine · 2022Article
- A murine cellular model of necroinflammation displays RAGE-dependent cytokine induction that connects to hepatoma cell injury.Journal of cellular and molecular medicine · 2020Article
- New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis.Scientific reports · 2020Article
- Macrophage-derived IL-1α promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity.Cellular & molecular immunology · 2018Article
- Acetaminophen Toxicity: Novel Insights Into Mechanisms and Future Perspectives.Gene expression · 2018Review
- New insights into Nod-like receptors (NLRs) in liver diseases.International journal of physiology, pathophysiology and pharmacology · 2018Review
- The Role of Monocytes and Macrophages in Acute and Acute-on-Chronic Liver Failure.Frontiers in immunology · 2018Review
- Anti-Inflammatory Effect of a Polyphenol-Enriched Fraction fromOxidative medicine and cellular longevity · 2018Article
- A Prominent Role of Interleukin-18 in Acetaminophen-Induced Liver Injury Advocates Its Blockage for Therapy of Hepatic Necroinflammation.Frontiers in immunology · 2018Article
- Extract from Mulberry (Morus australis) leaf decelerate acetaminophen induced hepatic inflammation involving downregulation of myeloid differentiation factor 88 (MyD88) signals.Journal of food and drug analysis · 2017Article
- Hepatic mitochondrial DNA/Toll-like receptor 9/MicroRNA-223 forms a negative feedback loop to limit neutrophil overactivation and acetaminophen hepatotoxicity in mice.Hepatology (Baltimore, Md.) · 2017Article
- Article
- Central role of the TIR-domain-containing adaptor-inducing interferon-β (TRIF) adaptor protein in murine sterile liver injury.Hepatology (Baltimore, Md.) · 2017Article
- Type I Interferon Supports Inducible Nitric Oxide Synthase in Murine Hepatoma Cells and Hepatocytes and during Experimental Acetaminophen-Induced Liver Damage.Frontiers in immunology · 2017Article
- Interferon β (IFN-β) Production during the Double-stranded RNA (dsRNA) Response in Hepatocytes Involves Coordinated and Feedforward Signaling through Toll-like Receptor 3 (TLR3), RNA-dependent Protein Kinase (PKR), Inducible Nitric Oxide Synthase (iNOS), and Src Protein.The Journal of biological chemistry · 2016Article
- Article
- A Novel Resolvin-Based Strategy for Limiting Acetaminophen Hepatotoxicity.Clinical and translational gastroenterology · 2016Article
- STAT3, a Key Parameter of Cytokine-Driven Tissue Protection during Sterile Inflammation - the Case of Experimental Acetaminophen (Paracetamol)-Induced Liver Damage.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Toll-like receptor (TLR) activation has been implicated in acetaminophen (APAP)-induced hepatotoxicity. Herein, we hypothesize that TLR3 activation significantly contributed to APAP-induced liver injury. In fasted wildtype (WT) mice, APAP caused significant cellular necrosis, edema, and inflammation in the liver, and the de novo expression and activation of TLR3 was found to be necessary for APAP-induced liver failure. Specifically, liver tissues from similarly fasted TLR3-deficient (tlr3(-/-) ) mice exhibited significantly less histological and biochemical evidence of injury after APAP challenge. Similar protective effects were observed in WT mice in which TLR3 was targeted through immunoneutralization at 3 h post-APAP challenge. Among three important death ligands (i.e. TNFα, TRAIL, and FASL) known to promote hepatocyte death after APAP challenge, TNFα was the only ligand that was significantly reduced in APAP-challenged tlr3(-/-) mice compared with APAP-challenged WT controls. In vivo studies demonstrated that TLR3 activation contributed to TNFα production in the liver presumably via F4/80(+) and CD11c(+) immune cells. In vitro studies indicated that there was cooperation between TNFα and TLR3 in the activation of JNK signaling in isolated and cultured liver epithelial cells (i.e. nMuLi). Moreover, TLR3 activation enhanced the expression of phosphorylated JNK in APAP injured livers. Thus, the current study demonstrates that TLR3 activation contributes to APAP-induced hepatotoxicity.
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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.