ArticleInternational journal of molecular sciences2016
Intra-Peritoneal Administration of Mitochondrial DNA Provokes Acute Lung Injury and Systemic Inflammation via Toll-Like Receptor 9.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Association between circulating cell-free mitochondrial DNA and inflammation factors in noninfectious diseases: A systematic review.PloS one · 2024Pooled it
- Stress and circulating cell-free mitochondrial DNA: A systematic review of human studies, physiological considerations, and technical recommendations.Mitochondrion · 2021Pooled it
- Psychological stress induced mitochondrial response in humans and its medial prefrontal biomarker correlates.Translational psychiatry · 2026Article
- Therapeutic Potential of Ginkgolic Acid C17:1 in Modulating PTEN/mtDNA/TLR9 Axis for Alleviating Chronic Pseudomonas Aeruginosa Infection in Bronchiectasis.Iranian journal of biotechnology · 2026Article
- Role of oxidative stress in sepsis: Mechanisms, pathways, and therapeutic strategies.Journal of pharmaceutical analysis · 2026Review
- The central role of mitochondrial pathology in sepsis-induced cardiomyopathy: from molecular mechanisms to clinical translation.Frontiers in cardiovascular medicine · 2026Review
- Cell-free mitochondrial DNA (cf-mtDNA) in human body fluids: molecular characteristics, release mechanisms, and clinical translation-an updated review.Frontiers in molecular biosciences · 2026Review
- Neutrophil-T cell cross talk in noninfectious liver diseases.American journal of physiology. Gastrointestinal and liver physiology · 2026Review
- MitoQ in sepsis-associated acute lung injury: redox pharmacology, mechanistic evidence, and translational perspectives.Frontiers in pharmacology · 2026Review
- Mitochondrial DNA release via mPTP and BAX/BAK drives inflammatory injury in intestinal ischemia reperfusion.Cell communication and signaling : CCS · 2025Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- NETosis in myocardial ischemia-reperfusion injury: From mechanisms to therapies (Review).Biomedical reports · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- Cell-free DNA: a metabolic byproduct with diagnostic and prognostic potential in rheumatic disorders.Frontiers in pharmacology · 2025Review
- Mitochondrial DNA Copy Number, a Damage-Associated Molecular Pattern Molecule, Can Predict Pancreatic Necrosis and Is Correlated with the Severity of Acute Pancreatitis.Digestive diseases and sciences · 2023Article
- Effects ofNutrition research and practice · 2023Article
- Fracture healing in a polytrauma rat model is influenced by mtDNA:cGAS complex mediated pro-inflammation.Journal of experimental orthopaedics · 2023Article
- Activation of cell-free mtDNA-TLR9 signaling mediates chronic stress-induced social behavior deficits.Molecular psychiatry · 2023Article
- Mitophagy-promoting miR-138-5p promoter demethylation inhibits pyroptosis in sepsis-associated acute lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation. Following LPS injection, plasma mtDNA copies peak at 8 h. Compared with wild-type (WT) mice, mtDNA in toll like receptor 4 knockout (TLR4 KO) mice were significantly decreased. MtDNA intra-peritoneal administration causes apparent ALI as demonstrated by increased lung injury score, bronchoalveolar lavage fluid (BALF) total protein and wet/dry (W/D) ratio; mtDNA injection also directly provokes systemic inflammation, as demonstrated by increased IL-1β, IL-6, high-mobility group protein B1 (HMGB1) level; while nuclear DNA (nDNA) could not induce apparent ALI and systemic inflammation. However, compared with WT mice, TLR4 KO could not protect from mtDNA induced ALI and systemic inflammation. Specific TLR9 inhibitor, ODN 2088 pretreatment can significantly attenuate mtDNA induced ALI and systemic inflammation, as demonstrated by improved lung injury score, decreased lung wet/dry ratio, BALF total protein concentration, and decreased systemic level of IL-1β, IL-6 and HMGB1. MtDNA administration activates the expression of p-P38 mitogen-activated protein kinases (MAPK) in lung tissue and specific TLR9 inhibitor pretreatment can attenuate this activation. Thus, LPS-induced mtDNA release occurs in a TLR4-dependent manner, and mtDNA causes acute lung injury and systemic inflammation in a TLR9-dependent and TLR4-independent manner.
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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.