ArticleFrontiers in immunology2021
Lactic Acid Fermentation Is Required for NLRP3 Inflammasome Activation.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Therapeutic potential of AdipoRon in cognitive, depressive, and anxiety disorders: a systematic review and meta-analysis.Molecular brain · 2026Pooled it
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Lactate acts as a metabolic brake on inflammation by repressing NLRP3 transcription via NF-κB inhibition.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- [Research progress on the metabolic regulatory mechanisms of coronary collateral circulation].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification.Cell death & disease · 2026Article
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- The NLRP3 Inflammasome in Neuropsychiatric Disorders: Molecular Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- The Lactate Nexus: A Molecular Bridge Linking Physical Activity, Sleep, and Cognitive Enhancement.Biomedicines · 2026Review
- The potential role of NLRP3 inflammasome in integrating redox, metabolic, and inflammatory signals during follicular development: a hypothesis-driven redox-metabolic integrator framework.Frontiers in cell and developmental biology · 2026Review
- Cuproptosis: A Potential Target for the Treatment of Systemic Lupus Erythematosus.Journal of inflammation research · 2026Review
- Lactate Metabolism and Protein Lactylation in Diabetic Kidney Disease: A Narrative Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- Revisiting osteoarthritis pathogenesis through the lens of cGAS-STING: Mitochondrial damage, pyroptosis, and inflammatory cascades.Journal of orthopaedic translation · 2026Review
- Macrophage Hypoxia Signaling Pathways and Their Roles in Sepsis.Journal of inflammation research · 2026Review
- Immunometabolic regulation in gouty arthritis: current evidence, mechanistic insights, and remaining challenges.Frontiers in immunology · 2026Review
- Bone Marrow Immunometabolic Remodeling in Osteoporosis: From Systemic Risk Factors to Precision Intervention.International journal of general medicine · 2026Review
- SIRT3 regulates PDHA1 acetylation in HUVECs to modulate inflammation and pyroptosis under clinorotation.iScience · 2025Article
- Gout Risk Allele RegulatingInternational journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the Nod-like receptor 3 (NLRP3) inflammasome is important for activation of innate immune responses, but improper and excessive activation can cause inflammatory disease. We previously showed that glycolysis, a metabolic pathway that converts glucose into pyruvate, is essential for NLRP3 inflammasome activation in macrophages. Here, we investigated the role of metabolic pathways downstream glycolysis - lactic acid fermentation and pyruvate oxidation-in activation of the NLRP3 inflammasome. Using pharmacological or genetic approaches, we show that decreasing lactic acid fermentation by inhibiting lactate dehydrogenase reduced caspase-1 activation and IL-1β maturation in response to various NLRP3 inflammasome agonists such as nigericin, ATP, monosodium urate (MSU) crystals, or alum, indicating that lactic acid fermentation is required for NLRP3 inflammasome activation. Inhibition of lactate dehydrogenase with GSK2837808A reduced lactate production and activity of the NLRP3 inflammasome regulator, phosphorylated protein kinase R (PKR), but did not reduce the common trigger of NLRP3 inflammasome, potassium efflux, or reactive oxygen species (ROS) production. By contrast, decreasing the activity of pyruvate oxidation by depletion of either mitochondrial pyruvate carrier 2 (MPC2) or pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) enhanced NLRP3 inflammasome activation, suggesting that inhibition of mitochondrial pyruvate transport enhanced lactic acid fermentation. Moreover, treatment with GSK2837808A reduced MSU-mediated peritonitis in mice, a disease model used for studying the consequences of NLRP3 inflammasome activation. Our results suggest that lactic acid fermentation is important for NLRP3 inflammasome activation, while pyruvate oxidation is not. Thus, reprograming pyruvate metabolism in mitochondria and in the cytoplasm should be considered as a novel strategy for the treatment of NLRP3 inflammasome-associated diseases.
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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.