NDLI: Upregulation of Interleukin 8 by Oxygen-deprived Cells in Glioblastoma Suggests a Role in Leukocyte Activation, Chemotaxis, and Angiogenesis

Content Provider	PubMed Central
Author	Desbaillets, Isabelle Diserens, Annie-claire Tribolet, Nicolas De Hamou, Marie-france Meir, Erwin G. van
Copyright Year	1997
Abstract	Leukocyte infiltration and necrosis are two biological phenomena associated with the development of neovascularization during the malignant progression of human astrocytoma. Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8–binding receptors in astrocytoma. IL-8 expression is first observed in low grade astrocytoma in perivascular tumor areas expressing inflammatory cytokines. In glioblastoma, it further localizes to oxygen-deprived cells surrounding necrosis. Hypoxic/anoxic insults on glioblastoma cells in vitro using anaerobic chamber systems or within spheroids developing central necrosis induced an increase in IL-8 messenger RNA (mRNA) and protein expression. mRNA for IL-8–binding chemokine receptors CXCR1, CXCR2, and the Duffy antigen receptor for chemokines (DARC) were found in all astrocytoma grades by reverse transcription/PCR analysis. In situ hybridization and immunohistochemistry localized DARC expression on normal brain and tumor microvascular cells and CXCR1 and CXCR2 expression to infiltrating leukocytes. These results support a model where IL-8 expression is initiated early in astrocytoma development through induction by inflammatory stimuli and later in tumor progression increases due to reduced microenvironmental oxygen pressure. Augmented IL-8 would directly and/or indirectly promote angiogenesis by binding to DARC and by inducing leukocyte infiltration and activation by binding to CXCR1 and CXCR2.
Starting Page	1201
File Format	PDF
ISSN	15409538
e-ISSN	15409538
Journal	The Journal of Experimental Medicine
Issue Number	8
Volume Number	186
Language	English
Publisher	The Rockefeller University Press
Publisher Date	1997-10-20
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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