Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells

Autor: Daniel Pérez-Cremades, Carlos Bueno-Betí, José Luis García-Giménez, José Santiago Ibañez-Cabellos, Federico V. Pallardó, Carlos Hermenegildo, Susana Novella
Rok vydání: 2022
Předmět:
Zdroj: Pérez Cremades, Daniel Bueno Betí, Carlos García Giménez, José Luis Ibáñez Cabellos, José Santiago Pallardó Calatayud, Federico Vicente Hermenegildo, Carlos Novella, Susana 2022 Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells. Journal of Physiology and Biochemistry
ISSN: 1877-8755
Popis: 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.
Databáze: OpenAIRE
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