IL-8 Directly Enhanced Endothelial Cell Survival, Proliferation, and Matrix Metalloproteinases Production and Regulated Angiogenesis | Zendy

Aihua Li | Zendy; Seema Dubey | Zendy; Michelle L. Varney | Zendy; Bhavana J. Davé | Zendy; Rakesh K. Singh | Zendy

Open Access

IL-8 Directly Enhanced Endothelial Cell Survival, Proliferation, and Matrix Metalloproteinases Production and Regulated Angiogenesis

Author(s) -

Aihua Li,

Seema Dubey,

Michelle L. Varney,

Bhavana J. Davé,

Rakesh K. Singh

Publication year - 2003

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.170.6.3369

Subject(s) - angiogenesis , matrix metalloproteinase , endothelial stem cell , microbiology and biotechnology , vascular endothelial growth inhibitor , vascular endothelial growth factor a , vascular endothelial growth factor c , interleukin 8 , biology , cxc chemokine receptors , vascular endothelial growth factor b , cell growth , chemokine , vascular endothelial growth factor , chemistry , cancer research , cytokine , immunology , in vitro , chemokine receptor , inflammation , biochemistry , vegf receptors

IL-8, a member of the chemokine family, has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective of this study was to determine the mechanism of IL-8-mediated angiogenesis. We examined the direct role of IL-8 in angiogenesis by examining IL-8 receptor expression on endothelial cells and their proliferation, survival, and matrix metalloproteinases (MMPs) production. We demonstrate that HUVEC and human dermal microvascular endothelial cells constitutively express CXCR1 and CXCR2 mRNA and protein. Recombinant human IL-8 induced endothelial cell proliferation and capillary tube organization while neutralization of IL-8 by anti-IL-8 Ab blocks IL-8-mediated capillary tube organization. Incubation of endothelial cells with IL-8 inhibited endothelial cell apoptosis and enhanced antiapoptotic gene expression. Endothelial cells incubated with IL-8 had higher levels of Bcl-x(L):Bcl-x(S) and Bcl-2:Bax ratios. Furthermore, incubation of endothelial cells with IL-8 up-regulated MMP-2 and MMP-9 production and mRNA expression. Our data suggest that IL-8 directly enhanced endothelial cell proliferation, survival, and MMP expression in CXCR1- and CXCR2-expressing endothelial cells and regulated angiogenesis.

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