| The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. | |
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MedLine Citation:
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PMID: 19752225 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inflammation and angiogenesis are pivotal processes in the progression of many diseases, including malignancies. A hypoxic microenvironment often results in a milieu of proinflammatory and proangiogenic cytokines produced by infiltrating cells. We assessed the role of macrophage-derived hypoxia-associated cytokines in promoting inflammation and angiogenesis. Supernatants of macrophages, stimulated under hypoxia with or without an inflammatory stimulus (LPS), promoted angiogenesis when incorporated into Matrigel plugs. However, neutralization of IL-1 in the supernatants, particularly IL-1beta, completely abrogated cell infiltration and angiogenesis in Matrigel plugs and reduced vascular endothelial growth factor (VEGF) levels by 85%. Similarly, supernatants from macrophages of IL-1beta knockout mice did not induce inflammatory or angiogenic responses. The importance of IL-1 signaling in the host was demonstrated by the dramatic reduction of inflammatory and angiogenic responses in Matrigel plugs that contained macrophage supernatants from control mice which had been implanted in IL-1 receptor type I knockout mice. Myeloid cells infiltrating into Matrigel plugs were of bone marrow origin and represented the major source of IL-1 and other cytokines/chemokines in the plugs. Cells of endothelial lineage were the main source of VEGF and were recruited mainly from neighboring tissues, rather than from the bone marrow. Using the aortic ring sprouting assay, it was shown that in this experimental system, IL-1 does not directly activate endothelial cell migration, proliferation and organization into blood vessel-like structures, but rather activates infiltrating cells to produce endothelial cell activating factors, such as VEGF. Thus, targeting IL-1beta has the potential to inhibit angiogenesis in pathological situations and may be of considerable clinical value. |
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Authors:
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Yaron Carmi; Elena Voronov; Shahar Dotan; Nitza Lahat; Michal A Rahat; Mina Fogel; Monika Huszar; Malka R White; Charles A Dinarello; Ron N Apte |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-09-14 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 183 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-21 Completed Date: 2009-11-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 4705-14 Citation Subset: AIM; IM |
Affiliation:
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The Shraga Segal Department of Microbiology and Immunology and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenic Proteins
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antagonists & inhibitors,
deficiency,
physiology* Animals Cell Migration Inhibition / immunology* Cells, Cultured Collagen / physiology Drug Combinations Endothelial Cells / cytology, immunology, metabolism Inflammation Mediators / physiology Interleukin-1alpha / deficiency, genetics, physiology* Interleukin-1beta / antagonists & inhibitors, deficiency, physiology* Laminin / physiology Lipopolysaccharides / physiology Macrophages, Peritoneal / immunology*, metabolism*, secretion Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Myeloid Cells / cytology, immunology, metabolism Neovascularization, Pathologic / immunology, pathology Neovascularization, Physiologic / genetics, immunology* Proteoglycans / physiology Vascular Endothelial Growth Factor A / antagonists & inhibitors, biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
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AI-15614/AI/NIAID NIH HHS; CA-04 6934/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenic Proteins; 0/Drug Combinations; 0/Inflammation Mediators; 0/Interleukin-1alpha; 0/Interleukin-1beta; 0/Laminin; 0/Lipopolysaccharides; 0/Proteoglycans; 0/Vascular Endothelial Growth Factor A; 119978-18-6/matrigel; 9007-34-5/Collagen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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