ArticleJournal of physiology and biochemistry2023
Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells.
Article in Journal of physiology and biochemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Basophil Extracellular Traps in Immunity and Disease.Cancers · 2026Review
- Article
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Toxic Alpha-Synuclein and the Opening of the Gate: Blood-Brain Barrier Damage and Stepwise Leukocyte Infiltration.Cellular and molecular neurobiology · 2026Review
- Review
- Role of oxidative stress in sepsis: Mechanisms, pathways, and therapeutic strategies.Journal of pharmaceutical analysis · 2026Review
- Current Insights into Clinical, Molecular, and Therapeutic Approaches to Acute Respiratory Distress Syndrome.Medical sciences (Basel, Switzerland) · 2026Review
- Activation of the cGAS-STING Pathway by NETs Promotes Inflammatory Injury in Myocardial Ischemia-Reperfusion.Journal of inflammation research · 2026Article
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- A Narrative Review on Nitrate-Rich Diets as Adjuncts to Antihypertensive Therapy: Enhancing Treatment Efficacy via Oxidative Stress Modulation.Biomedicines · 2025Review
- CircSARS-CV2-N1368 from SARS-CoV-2 impairs endothelial cell function through the upregulation of ATF7 to activate TLR4/NF-κB/ROS signaling.Acta pharmacologica Sinica · 2025Article
- Tandem ssDNA in neutrophil extracellular traps binds thrombin and regulates immunothrombosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endothelial Reactive Oxygen Species: Key Players in Cardiovascular Health and Disease.Antioxidants & redox signaling · 2025Review
- Unfractionated heparin attenuated histone-induced pulmonary endothelial glycocalyx injury through Ang/Tie2 pathway.Journal of inflammation (London, England) · 2025Article
- Skincare Benefits of a Postbiotic Ferment Produced Through Djon Djon Mushroom Fermentation by Saccharomyces.Journal of cosmetic dermatology · 2025Article
- The EZH2 Inhibitor GSK126 Alleviates Thromboinflammation in Deep Vein Thrombosis by Suppressing TLR4 Signaling via H3K27me3 Modulation.Journal of inflammation research · 2025Article
- Transcriptome combined single-cell sequencing explores molecular mechanisms of ANGPTL4 in sepsis-induced acute lung injury.PloS one · 2025Article
- The Effect of Hydroxysafflor Yellow A on Inflammatory Injury in LPS-induced Endothelial Cell Injury Model through TLR4/NF-κB Pathway Based on Network Pharmacology and Experimental Verification.Current pharmaceutical biotechnology · 2025Article
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- The effect of neutrophil extracellular traps in venous thrombosis.Thrombosis journal · 2023Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Extracellular histones have been reported to aggravate different pathophysiological processes by increasing vascular permeability, coagulopathy, and inflammation. In the present study, we elucidate how extracellular histones (10-100 µg/mL) concentration dependently increase cytosolic reactive oxygen species (ROS) production using human umbilical vein endothelial cells (HUVECs). Furthermore, we identify cyclooxygenase (COX) and NADPH oxidase (NOX) activity as sources of ROS production in extracellular histone-treated HUVEC. This COX/NOX-mediated ROS production is also involved in enhanced NF-kB activity and cell adhesion molecules (VCAM1 and ICAM1) expression in histone-treated HUVEC. Finally, by using different toll-like receptor (TLR) antagonists, we demonstrate the role of TLR4 in CAMs overexpression triggered by extracellular histones in endothelial cells. In conclusion, our data suggest that through TLR4 signaling, extracellular histones increase endothelial cell activation, a mechanism involving increased COX- and NOX-mediated ROS. These findings increase our understanding on how extracellular histones enhance systemic inflammatory responses in diseases in which histone release occurs as part of the pathological processes.
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Registered trials
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