Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells
J. physiol. biochem
; 79(2)may. 2023. graf, ilus
Artículo
en Inglés
| IBECS
| ID: ibc-222539
Biblioteca responsable:
ES1.1
Ubicación: ES15.1 - BNCS
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 (10100 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. (AU)
Texto completo:
Disponible
Colección:
Bases de datos nacionales
/
España
Base de datos:
IBECS
Asunto principal:
Histonas
/
FN-kappa B
Límite:
Humanos
Idioma:
Inglés
Revista:
J. physiol. biochem
Año:
2023
Tipo del documento:
Artículo
Institución/País de afiliación:
University of Valencia/Spain