Angiogenesis

, Volume 8, Issue 1, pp 63–71 | Cite as

Autocrine Role of Interleukin-8 in Induction of Endothelial Cell Proliferation, Survival, Migration and MMP-2 Production and Angiogenesis

  • Aihua Li
  • Michelle L. Varney
  • Jason Valasek
  • Maurice Godfrey
  • Bhavana J. Dave
  • Rakesh K. Singh
Article

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.

Keywords

angiogenesis apoptosis IL-8 CXCR1 CXCR2 endothelial cells chemokines 

Abbreviations

IL-8

interleukin-8

HUVEC

human umbilical vein endothelial cells

HMEC

human dermal microvascular endothelial cell

RT-PCR

reverse transcriptase-polymerase chain reaction

MMPs

matrix metalloproteinases

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Copyright information

© Springer 2005

Authors and Affiliations

  • Aihua Li
    • 1
  • Michelle L. Varney
    • 1
  • Jason Valasek
    • 2
  • Maurice Godfrey
    • 2
  • Bhavana J. Dave
    • 1
    • 2
  • Rakesh K. Singh
    • 1
  1. 1.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmaha
  2. 2.Department of PediatricsUniversity of Nebraska Medical CenterOmahaUSA

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