ArticleMolecular medicine (Cambridge, Mass.)2015
Toll-like receptor 4 (TLR4) antagonist eritoran tetrasodium attenuates liver ischemia and reperfusion injury through inhibition of high-mobility group box protein B1 (HMGB1) signaling.
Article in Molecular medicine (Cambridge, Mass.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 77 citations in OpenAlex.
- Tellurium Nanoparticles in Biomedicine: Harnessing a "Jekyll and Hyde" Element for Therapy and Diagnosis.Biological trace element research · 2026Review
- Damage-associated molecular patterns in hepatic ischemia-reperfusion injury: spatiotemporal signatures, biomarker potential, and clinical translation.Frontiers in immunology · 2026Review
- Sterile Inflammation and Cell Death Pathways in Liver Ischemia-Reperfusion Injury: A Review and Perspective.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Damage-associated molecular patterns (DAMPs) in diseases: implications for therapy.Molecular biomedicine · 2025Review
- Mechanism of action of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome and its regulation in liver injury.Chinese medical journal · 2025Review
- lncRNA CASC7 contributes to the progression of LPS-induced liver injury by targeting miRNA-217/TLR4 axis.Biomolecules & biomedicine · 2025Article
- Anti-DAMP therapies for acute inflammation.Frontiers in immunology · 2025Review
- Emerging Roles of High-mobility Group Box-1 in Liver Disease.Journal of clinical and translational hepatology · 2024Review
- Combined bacterial translocation and cholestasis aggravates liver injury by activation pyroptosis in obstructive jaundice.Heliyon · 2024Article
- Enhancing acute inflammatory and sepsis treatment: superiority of membrane receptor blockade.Frontiers in immunology · 2024Review
- Analyzing the Role of Specific Damage-Associated Molecular Patterns-Related Genes in Osteoarthritis and Investigating the Association between β-Amyloid and Apolipoprotein E Isoforms.Journal of innate immunity · 2024Article
- Responses of hepatic sinusoidal cells to liver ischemia-reperfusion injury.Frontiers in cell and developmental biology · 2023Review
- Innate immune modulation in transplantation: mechanisms, challenges, and opportunities.Frontiers in transplantation · 2023Review
- Ac2‑26 alleviates hepatic ischemia‑reperfusion injury based on inhibiting the positive feedback loop of HMGB1/TLR4/NF‑κB/neutrophils.Experimental and therapeutic medicine · 2022Article
- Liver ischaemia-reperfusion injury: a new understanding of the role of innate immunity.Nature reviews. Gastroenterology & hepatology · 2022Review
- Eritoran Attenuates Hepatic Inflammation and Fibrosis in Mice with Chronic Liver Injury.Cells · 2021Article
- Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-κB AxisBalkan medical journal · 2020Article
- Hepatic Macrophages in Liver Injury.Frontiers in immunology · 2020Review
- Mesenchymal Stromal Cells, a New Player in Reducing Complications From Liver Transplantation?Frontiers in immunology · 2020Review
- Remote Ischemic Preconditioning and Diazoxide Protect from Hepatic Ischemic Reperfusion Injury by Inhibiting HMGB1-Induced TLR4/MyD88/NF-κB Signaling.International journal of molecular sciences · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
Toll-like receptor 4 (TLR4) is ubiquitously expressed on parenchymal and immune cells of the liver and is the most studied TLR responsible for the activation of proinflammatory signaling cascades in liver ischemia and reperfusion (I/R). Since pharmacological inhibition of TLR4 during the sterile inflammatory response of I/R has not been studied, we sought to determine whether eritoran, a TLR4 antagonist trialed in sepsis, could block hepatic TLR4-mediated inflammation and end organ damage. When C57BL/6 mice were pretreated with eritoran and subjected to warm liver I/R, there was significantly less hepatocellular injury compared to control counterparts. Additionally, we found that eritoran is protective in liver I/R through inhibition of high-mobility group box protein B1 (HMGB1)-mediated inflammatory signaling. When eritoran was administered in conjunction with recombinant HMGB1 during liver I/R, there was significantly less injury, suggesting that eritoran blocks the HMGB1-TLR4 interaction. Not only does eritoran attenuate TLR4-dependent HMGB1 release in vivo, but this TLR4 antagonist also dampened HMGB1's release from hypoxic hepatocytes in vitro and thereby weakened HMGB1's activation of innate immune cells. HMGB1 signaling through TLR4 makes an important contribution to the inflammatory response seen after liver I/R. This study demonstrates that novel blockade of HMGB1 by the TLR4 antagonist eritoran leads to the amelioration of liver injury.
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