Hartman Institute for Therapeutic Organ Regeneration

Interleukin-1alpha promotes angiogenesis in vivo via VEGFR-2 pathway by inducing inflammatory cell VEGF synthesis and secretion.

TitleInterleukin-1alpha promotes angiogenesis in vivo via VEGFR-2 pathway by inducing inflammatory cell VEGF synthesis and secretion.
Publication TypeJournal Article
Year of Publication2002
AuthorsSalven P, Hattori K, Heissig B, Rafii S
JournalFASEB J
Volume16
Issue11
Pagination1471-3
Date Published2002 Sep
ISSN1530-6860
KeywordsAlternative Splicing, Animals, Blood Vessels, Cells, Cultured, Dose-Response Relationship, Drug, Endothelial Growth Factors, Humans, Interleukin-1, Leukocytes, Mononuclear, Lymphokines, Mice, Models, Biological, Neovascularization, Physiologic, Receptor Protein-Tyrosine Kinases, Receptors, Growth Factor, Receptors, Vascular Endothelial Growth Factor, RNA, Messenger, Signal Transduction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors
Abstract

During inflammation, functional changes occur in the vasculature, including extensive endothelial cell mitotic activity and remodeling of capillaries. Interleukin-1alpha (IL-1alpha)is a prototypical proinflammatory cytokine. Vascular endothelial growth factor (VEGF) is a strong endothelial cell-specific mitogen that exerts a pivotal role in angiogenesis under physiological and pathological conditions. We show that IL-1alpha stimulates VEGF secretion by human peripheral blood mononuclear cells (PBMNCs) in a dose-dependent manner. This represents induction of de novo VEGF synthesis, as an induction of VEGF mRNA was observed. Also, the release of VEGF was blocked by cycloheximide. Reverse transcription-polymerase chain reaction (RT-PCR) detected four VEGF splice variants in unstimulated and in IL-1alpha-stimulated PBMNCs. In vivo in mice, subcutaneously administered IL-1alpha caused a strong local angiogenic response, which was accompanied by an infiltrate of VEGF-expressing inflammatory cells. The angiogenic effect of IL-1a was blocked when the mice were treated with VEGF receptor 2 (VEGFR-2) neutralizing antibodies. VEGFR-1 blocking antibodies had a marginal inhibitory effect on IL-1alpha-induced angiogenesis. These observations indicate that IL-1alpha induces angiogenesis by activating the VEGF-VEGFR-2 signaling pathway between inflammatory cells and blood vessel endothelial cells. This novel mechanism of IL-1alpha-action may enhance the shift to angiogenic phenotype in various conditions designated by excessive angiogenesis.

DOI10.1096/fj.02-0134fje
Alternate JournalFASEB J
PubMed ID12205052

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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