Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis

• Published in: Angiogenesis (London) 2005-03, Vol.8 (1), p.63-71
• Main Authors: AIHUA LI, VARNEY, Michelle L, VALASEK, Jason, GODFREY, Maurice, DAVE, Bhavana J, SINGH, Rakesh K
• Format: Article
• Language: English
• Subjects: Autocrine Communication - physiology; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cell Line; Cell Movement; Cell Proliferation; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - cytology; Fundamental and applied biological sciences. Psychology; Humans; Interleukin-8 - immunology; Interleukin-8 - physiology; Matrix Metalloproteinase 2 - biosynthesis; Medical sciences; Neovascularization, Physiologic - physiology; Receptors, Interleukin-8A - immunology; Receptors, Interleukin-8B - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Tissue Inhibitor of Metalloproteinase-1; Tobacco, tobacco smoking; Toxicology; Vertebrates: cardiovascular system
• ISSN: 0969-6970; 1573-7209
• DOI: 10.1007/s10456-005-5208-4

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.