ArticleThe Journal of biological chemistry2013
Sterile inflammation in acetaminophen-induced liver injury is mediated by Cot/tpl2.
Article in The Journal of biological chemistry, 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, 46 citations in OpenAlex.
- Underlying mechanisms and treatment of acetaminophen‑induced liver injury (Review).Molecular medicine reports · 2025Review
- Hepatocyte-Specific Deficiency of BAP31 Amplified Acetaminophen-Induced Hepatotoxicity via Attenuating Nrf2 Signaling Activation in Mice.International journal of molecular sciences · 2021Article
- The complex roles of neutrophils in APAP-induced liver injury.Cell proliferation · 2021Review
- Rutaecarpine Protects against Acetaminophen-Induced Acute Liver Injury in Mice by Activating Antioxidant Enzymes.Antioxidants (Basel, Switzerland) · 2021Article
- Tpl2 Ablation Leads to Hypercytokinemia and Excessive Cellular Infiltration to the Lungs During Late Stages of Influenza Infection.Frontiers in immunology · 2021Article
- Bioinformatics-Based Analysis of the lncRNA-miRNA-mRNA Network and TF Regulatory Network to Explore the Regulation Mechanism in Spinal Cord Ischemia/Reperfusion Injury.Frontiers in genetics · 2021Article
- microRNA-381-3p Confers Protection Against Ischemic Stroke Through Promoting Angiogenesis and Inhibiting Inflammation by Suppressing Cebpb and Map3k8.Cellular and molecular neurobiology · 2020Article
- Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury.Stem cell research & therapy · 2020Review
- Cardamonin Reduces Acetaminophen-Induced Acute Liver Injury in Mice via Activating Autophagy and NFE2L2 Signaling.Frontiers in pharmacology · 2020Article
- IL-1α promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria.Scientific reports · 2019Article
- Astragaloside IV Attenuates Acetaminophen-Induced Liver Injuries in Mice by Activating the Nrf2 Signaling Pathway.Molecules (Basel, Switzerland) · 2018Article
- SIRT1 Controls Acetaminophen Hepatotoxicity by Modulating Inflammation and Oxidative Stress.Antioxidants & redox signaling · 2018Article
- Dual role of protein tyrosine phosphatase 1B in the progression and reversion of non-alcoholic steatohepatitis.Molecular metabolism · 2018Article
- Tpl2 Promotes Innate Cell Recruitment and Effector T Cell Differentiation To Limit Citrobacter rodentium Burden and Dissemination.Infection and immunity · 2017Article
- Severe Dermatitis Associated with SpontaneousComparative medicine · 2017Article
- Tpl2 promotes neutrophil trafficking, oxidative burst, and bacterial killing.Journal of leukocyte biology · 2017Article
- Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes.Archives of toxicology · 2016Article
- Deletion of tumor progression locus 2 attenuates alcohol-induced hepatic inflammation.Hepatobiliary surgery and nutrition · 2016Article
- Genetic and pharmacologic inhibition of Tpl2 kinase is protective in a mouse model of ventilator-induced lung injury.Intensive care medicine experimental · 2014Article
- Immune mechanisms in acetaminophen-induced acute liver failure.Hepatobiliary surgery and nutrition · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cot/tpl2 (MAP3K8) activates MKK1/2-Erk1/2 following stimulation of the Toll-like/IL-1 receptor superfamily. Here, we investigated the role of Cot/tpl2 in sterile inflammation and drug-induced liver toxicity. Cot/tpl2 KO mice exhibited reduced hepatic injury after acetaminophen challenge, as evidenced by decreased serum levels of both alanine and aspartate aminotransferases, decreased hepatic necrosis, and increased survival relative to Wt mice. Serum levels of both alanine and aspartate aminotransferases were also lower after intraperitoneal injection of acetaminophen in mice expressing an inactive form of Cot/tpl2 compared with Wt mice, suggesting that Cot/tpl2 activity contributes to acetaminophen-induced liver injury. Furthermore, Cot/tpl2 deficiency reduced neutrophil and macrophage infiltration in the liver of mice treated with acetaminophen, as well as their hepatic and systemic levels of IL-1α. Intraperitoneal injection of damage-associated molecular patterns from necrotic hepatocytes also impaired the recruitment of leukocytes and decreased the levels of several cytokines in the peritoneal cavity in Cot/tpl2 KO mice compared with Wt counterparts. Moreover, similar activation profiles of intracellular pathways were observed in Wt macrophages stimulated with Wt or Cot/tpl2 KO damage-associated molecular patterns. However, upon stimulation with damage-associated molecular patterns, the activation of Erk1/2 and JNK was deficient in Cot/tpl2 KO macrophages compared with their Wt counterparts; an effect accompanied by weaker release of several cytokines, including IL-1α, an important component in the development of sterile inflammation. Taken together, these findings indicate that Cot/tpl2 contributes to acetaminophen-induced liver injury, providing some insight into the underlying molecular mechanisms.
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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.