Title | Interleukin-1alpha promotes angiogenesis in vivo via VEGFR-2 pathway by inducing inflammatory cell VEGF synthesis and secretion. |
Publication Type | Journal Article |
Year of Publication | 2002 |
Authors | Salven P, Hattori K, Heissig B, Rafii S |
Journal | FASEB J |
Volume | 16 |
Issue | 11 |
Pagination | 1471-3 |
Date Published | 2002 Sep |
ISSN | 1530-6860 |
Keywords | Alternative 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. |
DOI | 10.1096/fj.02-0134fje |
Alternate Journal | FASEB J |
PubMed ID | 12205052 |