Vascular Endothelial Growth Factor Modulates Neutrophil Transendothelial Migration via Up-regulation of Interleukin-8 in Human Brain Microvascular Endothelial Cells

摘要: Hypoxia, a strong inducer for vascular endothelial growth factor (VEGF)/vascular permeable (VPF) expression, regulates leukocyte infiltration through the up-regulation of adhesion molecules and chemokine release. To determine whether VEGF/VPF is directly involved in secretion, we analyzed its effects on expression human brain microvascular cells (HBMECs) by using cytokine cDNA array kit. Cytokine analysis revealed significant increase monocyte chemoattractant protein-1 receptor CXCR4 HBMECs, result similar to that described previously other cells. Interestingly, also observed induced interleukin-8 (IL-8) HBMECs IL-8 mRNA was maximal after 1 h treatment Enzyme-linked immunosorbent assay data immunoprecipitation although at translational level basic fibroblast failed induce this protein within 12 h. increased production activation nuclear factor-KB via calcium phosphatidylinositol 3-kinase pathways, whereas ERK pathway not process. Supernatants VEGF/VPF-treated significantly neutrophil migration across HBMEC monolayer compared with those untreated control. Furthermore, addition anti-IL-8 antibody blocked migration, indicating functional HBMECs. Taken together, these demonstrate first time induces contributes chemokines, such as IL-8,