title: Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis.
abstract: 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.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Nebraska Medical Center, 985845, Omaha, Nebraska 68198-7660, USA.
authors.forename: Aihua
authors.initials: A
authors.lastname: Li
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Varney
authors.forename: Jason
authors.initials: J
authors.lastname: Valasek
authors.forename: Maurice
authors.initials: M
authors.lastname: Godfrey
authors.forename: Bhavana J
authors.initials: BJ
authors.lastname: Dave
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Singh
mesh_terms: 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
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2