Titre du document / Document title
CXCL8/IL8 Stimulates Vascular Endothelial Growth Factor (VEGF) Expression and the Autocrine Activation of VEGFR2 in Endothelial Cells by Activating NFKB through the CBM (Carma3/Bcl10/Malt1) Complex
Auteur(s) / Author(s)MARTIN Daniel
SILVIO GUTKIND J.
Résumé / Abstract
Vascular endothelial growth factor (VEGF) is a potent mitogen and permeability factor for endothelial cells that plays a central role in angiogenesis, vascular maintenance, inflammation, and cancer. VEGF also mediates the homeostatic adaptation to hypoxic conditions by promoting an increase in vascular density to compensate for decreased oxygenation. This process is triggered by an oxygen-sensitive transcription factor, hypoxia-inducible factor-1 (HIFIa), which becomes active in hypoxic tissues, leading to the synthesis and secretion of VEGF. The role of HIFIa in other processes that involve angiogenesis such as in inflammation is less clear. Of interest, endothelial cells not only respond to but also store and secrete VEGF, which is required for the maintenance of the integrity of the vascular system. How this intracellular pool of VEGF is regulated is still not understood. Here, we found that CXCL8/IL8, a potent proangiogenic and inflammatory chemokine, up-regulates VEGF mRNA and protein levels in endothelial cells by acting on its cognate receptor, CXCR2, and that this results in the autocrine activation of VEGFR2. Surprisingly, this process does not involve HIF1α but instead requires the activation of the transcription factor NFKB. Furthermore, we identified the components of the CBM complex, Carma3, Bcl10, and Maltl, as key mediators of the CXCL8/IL8-induced NFκB activation and VEGF up-regulation. Together, these findings support the existence of an NFκB-mediated pathway by which the proinflammatory chemokine CXCL8/IL8 controls the expression of VEGF in endothelial cells, thereby promoting the activation of VEGF receptors in an autocrine fashion.
Revue / Journal TitleThe Journal of biological chemistry
Source / Source
2009, vol. 284, no
10, pp. 6038-6042 [5 page(s) (article)]
Langue / Language
Editeur / Publisher
American Society for Biochemistry and Molecular Biology, Bethesda, MD, ETATS-UNIS
Localisation / Location
INIST-CNRS, Cote INIST : 3082, 35400018554551.0040
Nº notice refdoc (ud4) : 21224027