ArticleJournal of leukocyte biology2021
Classically activated mouse macrophages produce methylglyoxal that induces a TLR4- and RAGE-independent proinflammatory response.
Article in Journal of leukocyte biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Complex Contributions of Methylglyoxal to Pain, Axon Degeneration, and Diabetic Peripheral Neuropathy.Journal of neurochemistry · 2026Review
- Microbiota and Methylglyoxal-Derived AGEs: Implications in Ageing and Age-Related Disease.Life (Basel, Switzerland) · 2026Review
- Mitochondrial reactive oxygen species regulate HIF-1α stabilization and methylglyoxal accumulation in classically activated mouse macrophages.Immunometabolism (Cobham, Surrey) · 2026Review
- Methylglyoxal Accumulation is Associated with Brain Inflammation after Myocardial Infarction with Sex and Regional Differences.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Avoidance of MAIT cells is an essential determinant ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Host methylglyoxal activates theProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Polystyrene microplastic-induced pathophysiology is driven by disruption of efferocytosis.Immunity · 2026Article
- Role of Glycolysis and Nitric Oxide Pathway Crosstalk in Macrophages in Atherosclerosis.Current medicinal chemistry · 2026Review
- Methylglyoxal, a Knot to Be Untied in Brain Glucose Hypometabolism.Metabolites · 2025Review
- Methylglyoxal is an antibacterial effector produced by macrophages during infection.Cell host & microbe · 2025Article
- Atlas-scale metabolic activities inferred from single-cell and spatial transcriptomics.bioRxiv : the preprint server for biology · 2025Article
- Anserine reduces mortality in experimental sepsis by preventing methylglyoxal-induced capillary leakage.EBioMedicine · 2025Article
- Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α.Journal of leukocyte biology · 2025Article
- Article
- The role of AGEs in skeletal muscle atrophy and the beneficial effects of exercise.Frontiers in medicine · 2025Review
- Role of the Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Inflammatory Responses.Biomolecules · 2024Review
- Is Methylglyoxal a Potential Biomarker for the Warburg Effect Induced by the Lipopolysaccharide Neuroinflammation Model?Neurochemical research · 2024Article
- Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies.Molecules (Basel, Switzerland) · 2023Review
- Methylglyoxal suppresses microglia inflammatory response through NRF2-IκBζ pathway.Redox biology · 2023Article
- Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The highly reactive compound methylglyoxal (MG) can cause direct damage to cells and tissues by reacting with cellular macromolecules. MG has been identified as a biomarker associated with increased sepsis-induced mortality. Patients undergoing septic shock have significantly elevated circulating MG levels compared to postoperative patients and healthy controls. Furthermore, MG has been implicated in the development of type II diabetes mellitus and Alzheimer's disease. Because MG is generated during glycolysis, we hypothesized that MG may be produced by classically activated (M1) macrophages, possibly contributing to the inflammatory response. LPS and IFN-γ-treated macrophages acquired an M1 phenotype (as evidenced by M1 markers and enhanced glycolysis) and formed MG adducts, MG-H1, MG-H2, and MG-H3, which were detected using antibodies specific for MG-modified proteins (methylglyoxal 5-hydro-5-methylimidazolones). MG adducts were also increased in the lungs of LPS-treated mice. Macrophages treated with LPS and IFN-γ also exhibited decreased expression of glyoxalase 1 (Glo1), an enzyme that metabolizes MG. Concentrations of exogenous, purified MG > 0.5 mM were toxic to macrophages; however, a nontoxic dose of 0.3 mM induced TNF-α and IL-1β, albeit to a lesser extent than LPS stimulation. Despite prior evidence that MG adducts may signal through "receptor for advanced glycation endproducts" (RAGE), MG-mediated cell death and cytokine induction by exogenous MG was RAGE-independent in primary macrophages. Finally, RAGE-deficient mice did not exhibit a significant survival advantage following lethal LPS injection. Overall, our evidence suggests that MG may be produced by M1 macrophages during sepsis, following IFN-γ-dependent down-regulation of Glo1, contributing to over-exuberant inflammation.
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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.