IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis

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

Research output: Contribution to journalArticle

828 Citations (Scopus)

Abstract

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 metallo-proteinases (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-XL: Bcl-XS 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.

Original languageEnglish (US)
Pages (from-to)3369-3376
Number of pages8
JournalJournal of Immunology
Volume170
Issue number6
DOIs
StatePublished - Mar 15 2003

Fingerprint

Matrix Metalloproteinases
Interleukin-8
Cell Survival
Endothelial Cells
Cell Proliferation
Peptide Hydrolases
Interleukin-8B Receptors
Interleukin-8 Receptors
Organizations
Messenger RNA
Chemokines
Apoptosis
Neoplasm Metastasis
Gene Expression
Skin
Survival

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. / Li, Aihua; Dubey, Seema; Varney, Michelle L.; Dave, Bhavana J; Singh, Rakesh K.

In: Journal of Immunology, Vol. 170, No. 6, 15.03.2003, p. 3369-3376.

Research output: Contribution to journalArticle

@article{a4459856f5cb4842a8d6a600f2d4dd6f,
title = "IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis",
abstract = "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 metallo-proteinases (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-XL: Bcl-XS 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.",
author = "Aihua Li and Seema Dubey and Varney, {Michelle L.} and Dave, {Bhavana J} and Singh, {Rakesh K}",
year = "2003",
month = "3",
day = "15",
doi = "10.4049/jimmunol.170.6.3369",
language = "English (US)",
volume = "170",
pages = "3369--3376",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis

AU - Li, Aihua

AU - Dubey, Seema

AU - Varney, Michelle L.

AU - Dave, Bhavana J

AU - Singh, Rakesh K

PY - 2003/3/15

Y1 - 2003/3/15

N2 - 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 metallo-proteinases (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-XL: Bcl-XS 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.

AB - 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 metallo-proteinases (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-XL: Bcl-XS 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.

UR - http://www.scopus.com/inward/record.url?scp=0037443760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037443760&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.170.6.3369

DO - 10.4049/jimmunol.170.6.3369

M3 - Article

C2 - 12626597

AN - SCOPUS:0037443760

VL - 170

SP - 3369

EP - 3376

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -