Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells.
J Physiol Biochem
; 79(2): 251-260, 2023 May.
Article
en En
| MEDLINE
| ID: mdl-36464762
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Histonas
/
FN-kappa B
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Physiol Biochem
Asunto de la revista:
BIOQUIMICA
/
FISIOLOGIA
Año:
2023
Tipo del documento:
Article