ArticleToxicology and applied pharmacology2011
Macrophage activation by factors released from acetaminophen-injured hepatocytes: potential role of HMGB1.
Article in Toxicology and applied pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 73 citations in OpenAlex.
- Hepatocyte-Specific RORα Deficiency Accelerates Liver Regeneration by Unleashing ME1-Driven Glycolysis.Genes · 2026Article
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development.Frontiers in physiology · 2023Review
- Deer antler based active ingredients have protective effects on LPS/d-GalN-induced acute liver injury in mice through MAPK and NF-κB signalling pathways.Pharmaceutical biology · 2022Article
- Reappraisal of oxidized HMGB1 as a mediator and biomarker.Future science OA · 2022Review
- Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms.Frontiers in pharmacology · 2022Article
- Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- Review
- Recent Advances in Models of Immune-Mediated Drug-Induced Liver Injury.Frontiers in toxicology · 2021Review
- The role of RAGE in host pathology and crosstalk between RAGE and TLR4 in innate immune signal transduction pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Review
- New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis.Scientific reports · 2020Article
- Downregulation of Lysosomal Acid Ceramidase Mediates HMGB1-Induced Migration and Proliferation of Mouse Coronary Arterial Myocytes.Frontiers in cell and developmental biology · 2020Article
- Hepatic Macrophages in Liver Injury.Frontiers in immunology · 2020Review
- Spectrum of Microbial Sequences and a Bacterial Cell Wall Antigen in Primary Demyelination Brain Specimens Obtained from Living Patients.Scientific reports · 2019Article
- Pretreatment WithFrontiers in microbiology · 2019Article
- Methane Alleviates Acetaminophen-Induced Liver Injury by Inhibiting Inflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis through the Nrf2/HO-1/NQO1 Signaling Pathway.Oxidative medicine and cellular longevity · 2019Article
- Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives.Frontiers in pharmacology · 2019Review
- M2-like Kupffer cells in fibrotic liver may protect against acute insult.World journal of gastroenterology · 2017Article
- Experimental models of hepatotoxicity related to acute liver failure.Toxicology and applied pharmacology · 2016Review
- Mechanisms of fibrosis in acute liver failure.Liver international : official journal of the International Association for the Study of the Liver · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Toxic doses of acetaminophen (AA) cause hepatocellular necrosis. Evidence suggests that activated macrophages contribute to the pathogenic process; however, the factors that activate these cells are unknown. In these studies, we assessed the role of mediators released from AA-injured hepatocytes in macrophage activation. Treatment of macrophages with conditioned medium (CM) collected 24hr after treatment of mouse hepatocytes with 5mM AA (CM-AA) resulted in increased production of reactive oxygen species (ROS). Macrophage expression of heme oxygenase-1 (HO-1) and catalase mRNA was also upregulated by CM-AA, as well as cyclooxygenase (COX)-2 and 12/15-lipoxygenase (LOX). CM-AA also upregulated expression of the proinflammatory chemokines, MIP-1α and MIP-2. The effects of CM-AA on expression of COX-2, MIP-1α and MIP-2 were inhibited by blockade of p44/42 MAP kinase, suggesting a biochemical mechanism mediating macrophage activation. Hepatocytes injured by AA were found to release HMGB1, a potent macrophage activator. This was inhibited by pretreatment of hepatocytes with ethyl pyruvate (EP), which blocks HMGB1 release. EP also blocked CM-AA induced ROS production and antioxidant expression, and reduced expression of COX-2, but not MIP-1α or MIP-2. These findings suggest that HMGB1 released by AA-injured hepatocytes contributes to macrophage activation. This is supported by our observation that expression of the HMGB1 receptor RAGE is upregulated in macrophages in response to CM-AA. These data indicate that AA-injured hepatocytes contribute to the inflammatory environment in the liver through the release of mediators such as HMGB1. Blocking HMGB1/RAGE may be a useful approach to limiting classical macrophage activation and AA-induced hepatotoxicity.
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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.