Interleukin-1β augments the angiogenesis of endothelial progenitor cells in an NF-κB/CXCR7-dependent manner.

Abstract

Endothelial progenitor cells (EPCs) are able to trigger angiogenesis, and pro‐inflammatory cytokines have beneficial effects on angiogenesis under physiological and pathological conditions. C‐X‐C chemokine receptor type 7 (CXCR‐7), receptor for stromal cell‐derived factor‐1, plays a critical role in enhancing EPC angiogenic function. Here, we examined whether CXCR7 mediates the pro‐angiogenic effects of the inflammatory cytokine interleukin‐1β (IL‐1β) in EPCs. EPCs were isolated by density gradient centrifugation and angiogenic capability was evaluated in vitro by Matrigel capillary formation assay and fibrin gel bead assay. IL‐1β elevated CXCR7 expression at both the transcriptional and translational levels in a dose‐ and time‐dependent manner, and blockade of the nuclear translocation of NF‐κB dramatically attenuated the IL‐1β‐mediated up‐regulation of CXCR7 expression. IL‐1β stimulation significantly promoted EPCs tube formation and this effect was largely impaired by CXCR7‐siRNA transfection. IL‐1β treatment stimulated extracellular signal‐regulated kinase 1/2 (Erk1/2) phosphorylation, and inhibition of Erk1/2 phosphorylation partially impaired IL‐1β‐induced tube formation of EPCs but without significant effects on CXCR7 expression. Moreover, blocking NF‐κB had no significant effects on IL‐1β‐stimulated Erk1/2 phosphorylation. These findings indicate that CXCR7 plays an important role in the IL‐1β‐enhanced angiogenic capability of EPCs and antagonizing CXCR7 is a potential strategy for inhibiting angiogenesis under inflammatory conditions.