Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis.
Interleukin-8 (IL-8/CXCL8), a paracrine angiogenic factor, modulates multiple biologic functions in CXCR1 and CXCR2 expressing endothelial cells. Several reports suggest that inflammation, infection, cellular stress and tumor presence regulate IL-8 production in endothelial cells. In the present study, we test the hypothesis that IL-8 regulates multiple biological effects in endothelial cells in an autocrine manner. We examined the autocrine role of IL-8 in regulating angiogenesis by using a neutralizing antibody to IL-8, CXCR1 or CXCR2 in human vein umbilical endothelial cell (HUVEC) and human dermal microvascular endothelial cell (HMEC). Neutralizing antibody to IL-8, CXCR1 or CXCR2 inhibited endothelial cell proliferation, and MMP-2 production as compared to cells cultured with medium alone or control antibody. In addition, we observed that the number of apoptotic cells was significantly higher in anti-IL-8, anti-CXCR1 and anti-CXCR2 treated endothelial cells, which coincided with decreased survival-associated gene expression. We observed reduced migration of endothelial cells treated with anti-IL-8 and anti-CXCR2 antibody, but not anti-CXCR1 antibody as compared to controls. Further, we observed an inhibition of capillary tube formation and neovascularization following treatment with anti-IL-8, anti-CXCR1 and anti-CXCR2 antibodies. Together these data suggest that IL-8 functions as an important autocrine growth and angiogenic factor in regulating multiple biological activities in endothelial cells.
Li
Aihua
A
Department of Pathology and Microbiology, University of Nebraska Medical Center, Nebraska Medical Center, 985845, Omaha, Nebraska 68198-7660, USA.
Varney
Michelle L
ML
Valasek
Jason
J
Godfrey
Maurice
M
Dave
Bhavana J
BJ
Singh
Rakesh K
RK
D019898:Autocrine Communication / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D023062:Receptors, Interleukin-8A / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1
D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2