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

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.