ArticlePloS one2017
Self-extracellular RNA acts in synergy with exogenous danger signals to promote inflammation.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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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.
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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
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- Effects of Glucocorticoids on Postoperative Neurocognitive Disorders in Adult Patients: A Systematic Review and Meta-Analysis.Frontiers in aging neuroscience · 2022Pooled it
- Effect of dexmedetomidine on postoperative systemic inflammation and recovery in patients undergoing digest tract cancer surgery: A meta-analysis of randomized controlled trials.Frontiers in oncology · 2022Pooled it
- Improvement of Severe Fatigue Following Nuclease Therapy in Patients With Primary Sjögren's Syndrome: A Randomized Clinical Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- Neutrophil extracellular traps-associated candidate genes in IgA vasculitis: an exploratory multi-omics analysis integrating transcriptomics and Mendelian randomization.Pediatric rheumatology online journal · 2026Article
- Detection of Microbial Contamination in Nanomaterials Using LAL, rFC and Cell-Based Assays: Implications for Nanotoxicological Hazard Assessment.Nanomaterials (Basel, Switzerland) · 2025Article
- Extracellular RNA in iron-induced hepatic injury: Beyond TLR3 toward an integrated inflammatory axis.Toxicology reports · 2025Article
- Article
- Extracellular RNA and Endothelial TLR3 Link Inflammation and Venous Thromboembolism.Journal of the American Heart Association · 2024Article
- Photodynamic Therapy-Induced Anti-Tumor Immunity: Influence Factors and Synergistic Enhancement Strategies.Pharmaceutics · 2023Review
- Effect of Extracellular Ribonucleic Acids on Neurovascularization in Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Brain alarm by self-extracellular nucleic acids: from neuroinflammation to neurodegeneration.Journal of biomedical science · 2023Review
- New advances in clinical application of neostigmine: no longer focusing solely on increasing skeletal muscle strength.Frontiers in pharmacology · 2023Review
- Research Progress on Exosomes and MicroRNAs in the Microenvironment of Postoperative Neurocognitive Disorders.Neurochemical research · 2022Review
- Extracellular Ribosomal RNA Acts Synergistically with Toll-like Receptor 2 Agonists to Promote Inflammation.Cells · 2022Article
- Ribonuclease-1 treatment after traumatic brain injury preserves blood-brain barrier integrity and delays secondary brain damage in mice.Scientific reports · 2022Article
- Article
- Potential Neuroprotective Role of Sugammadex: A Clinical Study on Cognitive Function Assessment in an Enhanced Recovery After Cardiac Surgery Approach and an Experimental Study.Frontiers in cellular neuroscience · 2022Article
- Self-extracellular RNA promotes pro-inflammatory response of astrocytes to exogenous and endogenous danger signals.Journal of neuroinflammation · 2021Article
- Review: Ischemia Reperfusion Injury-A Translational Perspective in Organ Transplantation.International journal of molecular sciences · 2020Review
- Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis.Nature communications · 2020Article
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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Self-extracellular RNA (eRNA), released from stressed or injured cells upon various pathological situations such as ischemia-reperfusion-injury, has been shown to act as an alarmin by inducing procoagulatory and proinflammatory responses. In particular, M1-polarization of macrophages by eRNA resulted in the expression and release of a variety of cytokines, including tumor necrosis factor (TNF)-α or interleukin-6 (IL-6). The present study now investigates in which way self-eRNA may influence the response of macrophages towards various Toll-like receptor (TLR)-agonists. Isolated agonists of TLR2 (Pam2CSK4), TLR3 (PolyIC), TLR4 (LPS), or TLR7 (R848) induced the release of TNF-α in a concentration-dependent manner in murine macrophages, differentiated from bone marrow-derived stem cells by mouse colony stimulating factor. Here, the presence of eRNA shifted the dose-response curve for Pam2CSK4 (Pam) considerably to the left, indicating that eRNA synergistically enhanced the cytokine liberation from macrophages even at very low Pam-levels. The synergistic activation of TLR2 by eRNA/Pam was duplicated by other TLR2-agonists such as FSL-1 or Pam3CSK4. In contrast, for TLR4-agonists such as LPS a synergistic effect of eRNA was much weaker, and was not existent for TLR3-, or TLR7-agonists. The synergistic eRNA/Pam action was dependent on the NFκB-signaling pathway as well as on p38MAP- and MEK1/ERK-kinases and was prevented by predigestion of eRNA with RNase1 or by antibodies against TLR2. Thus, the presence of self-eRNA as alarming molecule sensitizes innate immune responses towards pathogen-associated molecular patterns (PAMPs) in a synergistic way and may thereby contribute to the differentiated outcome of inflammatory responses.
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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.