Portal de investigación
Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells
Fecha de publicación:
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Autores de INCLIVA
Participantes ajenos a INCLIVA
- Bueno-Beti, Carlos
- Ibanez-Cabellos, Jose Santiago
Grupos y Plataformas de I+D+i
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 mu g/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.
© 2022. The Author(s).
Datos de la publicación
- ISSN/ISSNe:
- 1138-7548, 1877-8755
- Tipo:
- Article
- Páginas:
- 251-260
- PubMed:
- 36464762
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY SPRINGER
Citas Recibidas en Web of Science: 22
Documentos
- No hay documentos
Filiaciones
Keywords
- Endothelium; Extracellular histones; Inflammation
Financiación
Proyectos y Estudios Clínicos
Sex- and estrogen-dependent regulation of miRNA in Acute Coronary Syndrome and functional impact on human endothelial cells. New biomarkers for primary prevention.
Investigador/a Principal CARLOS HERMENEGILDO CAUDEVILLA
PI19/01714 . INSTITUTO SALUD CARLOS III . 2020
