ArticleThe Journal of biological chemistry2013
Immune responsive gene 1 (IRG1) promotes endotoxin tolerance by increasing A20 expression in macrophages through reactive oxygen species.
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 112 papers.
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Who cites it
112 citing papers in PubMed.
- ACOD1 deficiency promotes DDX1 methylation-mediated mitochondrial dysfunction and dermal papilla cell senescence in androgenetic alopecia.BMC medicine · 2026Article
- LCN2-ACOD1 Signalling Affects the Post-Injury Regeneration of Skeletal Muscle Through Mediating Ferroptosis.Cell proliferation · 2026Article
- Next-Generation Redox Mediators: Itaconate, Nitro-Fatty Acids, Reactive Sulfur Species and Succinate as Emerging Switches in Predictive Redox Medicine.Antioxidants (Basel, Switzerland) · 2026Review
- Analysis of mRNA and miRNA expression in RAW 264.7 macrophages infected withFrontiers in veterinary science · 2026Article
- IRG1-itaconate axis in immunometabolism: mechanistic roles and therapeutic potential in inflammatory diseases.Frontiers in immunology · 2026Review
- Itaconate modulates myeloid inflammation in myocardial infarction via metabolic and structural reprogramming.Genes & genomics · 2026Article
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Profiling RNA subcellular localization in situ by TATA-seq.RNA (New York, N.Y.) · 2025Article
- Reprogramming immunity with itaconate: metabolic mechanisms and therapeutic perspectives.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Itaconic Acid: A Regulator of Immune Responses and Inflammatory Metabolism.Current issues in molecular biology · 2025Review
- Immunoresponsive gene 1 facilitates TLR4 agonist-induced augmentation of innate antimicrobial immunity.Journal of leukocyte biology · 2025Article
- High glucose induces pro-inflammatory polarization of macrophages by inhibiting immune-responsive gene 1 expression.Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Enhanced itaconic acid secretion from macrophages mediates the protection of mesenchymal stem cell-derived exosomes on lipopolysaccharide-induced acute lung injury mice.Biology direct · 2024Article
- Macrophage polarization and metabolic reprogramming in abdominal aortic aneurysm.Immunity, inflammation and disease · 2024Review
- Review
- IRG1/ACOD1 promotes neutrophil reverse migration and alleviates local inflammation.Journal of leukocyte biology · 2024Article
- The role and therapeutic potential of itaconate in lung disease.Cellular & molecular biology letters · 2024Review
- The Aconitate Decarboxylase 1/Itaconate Pathway Modulates Immune Dysregulation and Associates with Cardiovascular Disease Markers and Disease Activity in Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- 4-Octyl itaconate inhibits inflammation via the NLRP3 pathway in neuromyelitis optica spectrum disorders.Annals of clinical and translational neurology · 2024Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis-associated immunosuppression (SAIS) is regarded as one of main causes for the death of septic patients at the late stage because of the decreased innate immunity with a more opportunistic infection. LPS-tolerized macrophages, which are re-challenged by LPS after prior exposure to LPS, are regarded as the common model of hypo-responsiveness for SAIS. However, the molecular mechanisms of endotoxin tolerance and SAIS remain to be fully elucidated. In addition, negative regulation of the Toll-like receptor (TLR)-triggered innate inflammatory response needs further investigation. Here we show that expression of immune responsive gene 1 (IRG1) was highly up-regulated in the peripheral blood mononuclear cells of septic patients and in LPS-tolerized mouse macrophages. IRG1 significantly suppressed TLR-triggered production of proinflammatory cytokines TNF-α, IL-6, and IFN-β in LPS-tolerized macrophages, with the elevated expression of reactive oxygen species (ROS) and A20. Moreover, ROS enhanced A20 expression by increasing the H3K4me3 modification of histone on the A20 promoter domain, and supplement of the ROS abrogated the IRG1 knockdown function in breaking endotoxin tolerance by increasing A20 expression. Our results demonstrate that inducible IRG1 promotes endotoxin tolerance by increasing A20 expression through ROS, indicating a new molecular mechanism regulating hypoinflammation of sepsis and endotoxin tolerance.
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