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Cited by 476

The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.

Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2

Open access
Heidemann, Jan, Ogawa, Hitoshi, Dwinell, Michael B., Rafiee, Parvaneh, Maaser, Christian, Gockel, Henning R., Otterson, Mary F., Ota, David M., Lügering, Norbert, Domschke, Wolfram, Binion, David G.·2003·Journal of Biological Chemistry

Abstract

Angiogenesis plays a critical role in metastasis and tumor growth. Human tumors, including colorectal adenocarcinoma, secrete angiogenic factors, inducing proliferation and chemotaxis of microvascular endothelial cells, eventually leading to tumor neovascularization. The chemokine interleukin 8 (IL-8; CXCL8) exerts potent angiogenic properties on endothelial cells through interaction with its cognate receptors CXCR1 and CXCR2. As CXCR1 and CXCR2 expression is differentially regulated in tissue-specific endothelial cells and effects of IL-8 on intestinal endothelial cells are not defined, we characterized the potential IL-8-induced angiogenic mechanisms in primary cultures of human intestinal microvascular endothelial cells (HIMEC) and IL-8 receptor expression in human intestinal microvessels. CXCR1 and CXCR2 expression on HIMEC were defined using reverse transcriptase-PCR, immunohistochemistry, flow cytometry, and Western blot analysis. IL-8-induced downstream signaling events were assessed using immunoblot analysis and immunofluorescence. The angiogenic effects of IL-8 on HIMEC were determined using proliferation and chemotaxis assays. HIMEC responded to IL-8 with rapid stress fiber assembly, chemotaxis, enhanced proliferation, and phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2). HIMEC express CXCR2, but not CXCR1. Neutralizing antibodies to CXCR2 diminished IL-8-induced chemotaxis and stress fiber assembly. Specific inhibitors of ERK 1/2 and phosphoinositide 3-kinase abrogated endothelial tube formation and IL-8-induced chemotaxis in HIMEC. IL-8 elicits angiogenic responses in microvascular endothelial cells isolated from human intestine by engaging CXCR2. We confirmed tissue expression of CXCR2 in human intestinal microvessels. Supported by the notion that malignant colonic epithelial cells overexpress IL-8, CXCR2 blockade may be a novel target for anti-angiogenic therapy in colorectal adenocarcinoma.

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Metadata

Authors
Heidemann, J., Ogawa, H., Dwinell, M. B., Rafiee, P., Maaser, C., Gockel, H. R., Otterson, M. F., Ota, D. M., Lügering, N., Domschke, W., & Binion, D. G.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-03
Volume
278
Issue
10
Pages
8508-8515
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2135377650
Cited by
476
References
67
FWCI
8.03
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2. https://app.cochat.ai/papers/10.1074/jbc.m208231200
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Heidemann, J., Ogawa, H., Dwinell, M. B., Rafiee, P., Maaser, C., Gockel, H. R., Otterson, M. F., Ota, D. M., Lügering, N., Domschke, W., & Binion, D. G. (2003). Angiogenic Effects of Interleukin 8 (CXCL8) in Human Intestinal Microvascular Endothelial Cells Are Mediated by CXCR2. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m208231200

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