ArticleAmerican journal of respiratory and critical care medicine2008
Mitochondrial respiratory complex I regulates neutrophil activation and severity of lung injury.
Article in American journal of respiratory and critical care medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
111 citing papers in PubMed, 3 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Effects of metformin on acute respiratory distress syndrome in preclinical studies: a systematic review and meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Association of preadmission metformin use and mortality in patients with sepsis and diabetes mellitus: a systematic review and meta-analysis of cohort studies.Critical care (London, England) · 2019 · on this mapPooled it
- Pooled it
- Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Mitochondria Meet the Lung Microbiome: A Bidirectional Dialogue in Inflammation and Respiratory Diseases.Biomedicines · 2026Review
- Innate Immune Function of Neutrophil Cytoplasts Generated Post-Vital NETosis.Research square · 2026Article
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils.Science advances · 2025Article
- NDUFS1 upregulates ENaCα by NAD+ to promote alveolar fluid clearance in acute lung injury.International journal of medical sciences · 2025Article
- A Review on Risk Factors, Traditional Diagnostic Techniques, and Biomarkers for Pneumonia Prognostication and Management in Diabetic Patients.Diseases (Basel, Switzerland) · 2024Review
- ROS-responsive nanoparticles for bioimaging and treating acute lung injury by releasing dexamethasone and improving alveolar macrophage homeostasis.Journal of nanobiotechnology · 2024Article
- Research progress of mitochondrial dysfunction induced pyroptosis in acute lung injury.Respiratory research · 2024Review
- Not just sugar: metabolic control of neutrophil development and effector functions.Journal of leukocyte biology · 2024Review
- FTY720 ameliorates experimental MPO-ANCA-associated vasculitis by regulating fatty acid oxidation via the neutrophil PPARα-CPT1a pathway.Rheumatology (Oxford, England) · 2024Article
- The emerging role for neutrophil mitochondrial metabolism in lung inflammation.Immunometabolism (Cobham, Surrey) · 2024Review
- AMPK activation improves recovery from pneumonia-induced lung injury via reduction of er-stress and apoptosis in alveolar epithelial cells.Respiratory research · 2023Article
- Neutrophil (dys)function due to altered immuno-metabolic axis in type 2 diabetes: implications in combating infections.Human cell · 2023Review
- The emerging role for metabolism in fueling neutrophilic inflammation.Immunological reviews · 2023Review
- A metabolic perspective of the neutrophil life cycle: new avenues in immunometabolism.Frontiers in immunology · 2023Review
- MERS-CoV nsp1 impairs the cellular metabolic processes by selectively downregulating mRNAs in a novel granules.Virulence · 2022Article
51 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
8 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleMitochondria have important roles in intracellular energy generation, modulation of apoptosis, and redox-dependent intracellular signaling. Although reactive oxygen species (ROS) participate in the regulation of intracellular signaling pathways, including activation of nuclear factor (NF)-kappaB, there is only limited information concerning the role of mitochondrially derived ROS in modulating cellular activation and tissue injury associated with acute inflammatory processes.
objectivesTo examine involvement of the mitochondrial electron transport chain complex I on LPS-mediated NF-kappaB activation in neutrophils and neutrophil-dependent acute lung injury.
methodsNeutrophils incubated with rotenone or metformin were treated with bacterial lipopolysaccharide (LPS) to determine the effects of mitochondrial complex I inhibition on intracellular concentrations of reactive oxygen species, NF-kappaB activation, and proinflammatory cytokine expression. Acute lung injury was produced by intratracheal injection of LPS into control, metformin, or rotenone-treated mice. MEASUREMENTS AND MAIN
resultsInhibition of complex I with either rotenone or the antihyperglycemic agent metformin was associated with increased intracellular levels of both superoxide and hydrogen peroxide, as well as inhibition of LPS-induced I kappaB-alpha degradation, NF-kappaB nuclear accumulation, and proinflammatory cytokine production. Treatment of LPS-exposed mice with rotenone or metformin resulted in inhibition of complex I in the lungs, as well as diminished severity of lung injury.
conclusionsThese results demonstrate that mitochondrial complex I plays an important role in modulating Toll-like receptor 4-mediated neutrophil activation and suggest that metformin, as well as other agents that inhibit mitochondrial complex I, may be useful in the prevention or treatment of acute inflammatory processes in which activated neutrophils play a major role, such as acute lung injury.
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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.