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

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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.

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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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Authors and Affiliations

  1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Nebraska Medical Center, 985845, Omaha, Nebraska, USA

    Aihua Li, Michelle L. Varney, Bhavana J. Dave & Rakesh K. Singh

  2. Department of Pediatrics, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska, USA

    Jason Valasek, Maurice Godfrey & Bhavana J. Dave

Authors
  1. Aihua Li
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  2. Michelle L. Varney
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  3. Jason Valasek
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  4. Maurice Godfrey
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  5. Bhavana J. Dave
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  6. Rakesh K. Singh
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Correspondence to Rakesh K. Singh.

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Li, A., Varney, M., Valasek, J. et al. Autocrine Role of Interleukin-8 in Induction of Endothelial Cell Proliferation, Survival, Migration and MMP-2 Production and Angiogenesis. Angiogenesis 8, 63–71 (2005). https://doi.org/10.1007/s10456-005-5208-4

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  • DOI: https://doi.org/10.1007/s10456-005-5208-4

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