Opposite effects of HIF-1α and HIF-2α on the regulation of IL-8 expression in endothelial cells

► HIF-1 decreases whereas HIF-2 increases the expression of IL-8 in endothelial cells. ► SP-1 and c-Myc are involved in the HIF-2α-dependent IL-8 upregulation. ► Mxi-1, a c-Myc antagonist, mediates IL-8 diminishment by hypoxia/HIF-1α. ► Inhibition of Nrf2 activity by hypoxia/HIF-1α adds to the downregulation of IL-8. ► Both HIF isoforms are stabilized in hypoxia but the effect of HIF-1α is predominant.