ArticleCritical care medicine2015
Toll-like receptor 9 signaling regulates tissue factor and tissue factor pathway inhibitor expression in human endothelial cells and coagulation in mice.
Article in Critical care medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Impact of Toll-Like Receptor 2 and 9 Gene Polymorphisms on COVID-19: Susceptibility, Severity, and Thrombosis.Journal of inflammation research · 2023Article
- Role of Mesenchymal Stem/Stromal Cells in Coagulation.International journal of molecular sciences · 2022Review
- Review
- Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury.Journal of pathology and translational medicine · 2022Article
- Single Nucleotide Polymorphisms fromGenes · 2021Article
- BAY11-7082 inhibits the expression of tissue factor and plasminogen activator inhibitor-1 in type-II alveolar epithelial cells following TNF-α stimulation via the NF-κB pathway.Experimental and therapeutic medicine · 2021Article
- TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model.Diabetes · 2021Article
- Effect of miR-27b-5p on apoptosis of human vascular endothelial cells induced by simulated microgravity.Apoptosis : an international journal on programmed cell death · 2020Article
- TLR9 in MAFLD and NASH: At the Intersection of Inflammation and Metabolism.Frontiers in endocrinology · 2020Review
- TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target.Frontiers in pharmacology · 2020Article
- When Innate Immunity Meets Angiogenesis-The Role of Toll-Like Receptors in Endothelial Cells and Pulmonary Hypertension.Frontiers in medicine · 2020Review
- Toll-like receptors 2 and 7 mediate coagulation activation and coagulopathy in murine sepsis.Journal of thrombosis and haemostasis : JTH · 2019Article
- IKKβ regulates the expression of coagulation and fibrinolysis factors through the NF-κB canonical pathway in LPS-stimulated alveolar epithelial cells type II.Experimental and therapeutic medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveBacterial DNA (CpG DNA) persists in tissues and blood under pathological conditions that are associated with enhanced intravascular coagulation. Toll-like receptor 9 recognizes CpG DNA and elicits innate and adoptive immunity, yet the impact of CpG DNA on coagulation has not been studied. In this study, we investigated the effects of CpG DNA on the expression and activity of tissue factor, a key initiator of coagulation and tissue factor pathway inhibitor in human coronary artery endothelial cells and on coagulation in mice.
designControlled in vitro and in vivo studies.
settingUniversity research laboratory. SUBJECTS: Cultured human coronary artery endothelial cell, wild-type mice, and TLR9-deficient mice.
interventionsHuman coronary artery endothelial cell was challenged with CpG DNA, and tissue factor and tissue factor pathway inhibitor expression and activity were assessed. In mice, the effects of CpG DNA on bleeding time and plasma levels of thrombin-antithrombin complexes and tissue factor were measured. MEASUREMENTS AND MAIN
resultsWe found that CpG DNA, but not eukaryotic DNA, evoked marked nuclear factor-κB-mediated increases in tissue factor expression at both messenger RNA and protein levels, as well as in tissue factor activity. Conversely, CpG DNA significantly reduced tissue factor pathway inhibitor transcription, secretion, and activity. Inhibition of Toll-like receptor 9 with a telomere-derived Toll-like receptor 9 inhibitory oligonucleotide or transient Toll-like receptor 9 knockdown with small interfering RNA attenuated human coronary artery endothelial cell responses to CpG DNA. In wild-type mice, CpG DNA shortened the bleeding time parallel with dramatic increases in plasma thrombin-antithrombin complex and tissue factor levels. Pretreatment with inhibitory oligonucleotide or anti-tissue factor antibody or genetic deletion of TLR9 prevented these changes, whereas depleting monocytes with clodronate resulted in a modest partial inhibition.
conclusionsOur findings demonstrate that bacterial DNA through Toll-like receptor 9 shifted the balance of tissue factor and tissue factor pathway inhibitor toward procoagulant phenotype in human coronary artery endothelial cells and activated blood coagulation in mice. Our study identifies Toll-like receptor 9 inhibitory oligonucleotides as potential therapeutic agents for the prevention of coagulation in pathologies where bacterial DNA may abundantly be present.
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