ArticleImmunity2021
Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation.
Article in Immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
259 citing papers in PubMed, 2 syntheses or guidelines pooled it, 381 citations in OpenAlex.
- Impact of metformin on melanoma: a meta-analysis and systematic review.Frontiers in oncology · 2024Pooled it
- Metformin for Treatment of Acute COVID-19: Systematic Review of Clinical Trial Data Against SARS-CoV-2.Diabetes care · 2023Pooled it
- Metformin and Time to Sustained Recovery in Adults With COVID-19: The ACTIV-6 Randomized Clinical Trial.JAMA internal medicine · 2025Trial
- Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Olaparib Blocks Oxidative Stress-Dependent NLRP3 Inflammasome in Pediatric Acute Lung Injury by Metabolic Reprogramming via AMPK-Driven Autophagic Flux.The Kaohsiung journal of medical sciences · 2026Article
- Mitochondria-Targeted Multimodal Nanotherapeutics Suppress Oxidized mtDNA-Driven Inflammation at the Source.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Macrophage RSAD2 Couples mtDNA Synthesis With a Self-Amplifying Inflammatory Circuit to Orchestrate Tissue Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tetracycline-loaded nanomotors target neutrophil activation and oxidative stress in acute lung injury.iScience · 2026Article
- The landscape of protein post-translational modifications in the pathogenesis of acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Neuroimmune Regulation of NLRP3 Signalling in Parkinson's Disease.Molecular neurobiology · 2026Review
- Prior SGLT2 Inhibitor and Metformin Use and Risk of Long COVID in Type 2 Diabetes: A Nationwide Population-Based Cohort Study.Infectious diseases and therapy · 2026Article
- Pro-Inflammatory Vicious Cycle-Normalizing Biomimetic Nanoparticles to Treat Acute Respiratory Distress Syndrome.Advanced healthcare materials · 2026Article
- Endothelial cell-specific knockout of ATG5 ameliorates inflammation and renal fibrosis by regulating pyroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment.Cells · 2026Review
- Metformin and cRGDfc-Modified Nanoparticles Loaded with Curcumin for Age-Related Macular Degeneration: In Vitro Pharmacodynamics and Molecular Mechanisms.Pharmaceutics · 2026Article
- Sympathetic signaling activation alleviated acute respiratory distress syndrome via the HDC/SLC7A11 axis in lipopolysaccharide-induced macrophages.Cell death discovery · 2026Article
- Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.The Journal of biological chemistry · 2026Review
- Metformin improves endotoxemia and alters folliculogenesis in women with polycystic ovary syndrome.Endocrine connections · 2026Article
- Mitochondrial DNA release contributes to neuropathic pain via a cGAS-STING-IRF3-CMPK2-associated immunometabolic feedback mechanism.Journal of translational medicine · 2026Article
- Tristetraprolin protects against osteoarthritis by restraining chondrocyte mitochondrial DNA release through post-transcriptional regulation.Journal of orthopaedic translation · 2026Article
199 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Acute respiratory distress syndrome (ARDS), an inflammatory condition with high mortality rates, is common in severe COVID-19, whose risk is reduced by metformin rather than other anti-diabetic medications. Detecting of inflammasome assembly in post-mortem COVID-19 lungs, we asked whether and how metformin inhibits inflammasome activation while exerting its anti-inflammatory effect. We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1β production in cultured and alveolar macrophages along with inflammasome-independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS)- and SARS-CoV-2-induced ARDS. By targeting electron transport chain complex 1 and independently of AMP-activated protein kinase (AMPK) or NF-κB, metformin blocked LPS-induced and ATP-dependent mitochondrial (mt) DNA synthesis and generation of oxidized mtDNA, an NLRP3 ligand. Myeloid-specific ablation of LPS-induced cytidine monophosphate kinase 2 (CMPK2), which is rate limiting for mtDNA synthesis, reduced ARDS severity without a direct effect on IL-6. Thus, inhibition of ATP and mtDNA synthesis is sufficient for ARDS amelioration.
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What OpenQuestion holds
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.