Cutting edge: IL-1beta mediates the proangiogenic activity of osteopontin-activated human monocytes.
Inflammation plays an important role in the onset of angiogenesis. In the present study, we show that osteopontin (OPN), a proinflammatory mediator involved in tissue repair, induces IL-1beta up-regulation in human monocytes. This was accompanied by the enhanced production of TNF-alpha, IL-8, and IL-6, a decreased release of IL-10, and increased p38 phosphorylation. The supernatants of OPN-treated monocytes were highly angiogenic when delivered on the chick embryo chorioallantoic membrane. The angiogenic response was completely abrogated by a neutralizing anti-IL-1 Ab, thus indicating that this cytokine represents the major proangiogenic factor expressed by OPN-activated monocytes. Accordingly, rIL-1beta mimicked the proangiogenic activity of OPN-treated monocyte supernatants, and IL-1R (type I) was found to be expressed in the chorioallantoic membrane. In conclusion, OPN-activated monocytes may contribute to the onset of angiogenesis through a mechanism mediated by IL-1beta.
Naldini
Antonella
A
Unit of Neuroimmunophysiology, Department of Physiology, University of Siena, Via Aldo Moro, 53100 Siena, Italy. Naldini@Unisi.it
Leali
Daria
D
Pucci
Annalisa
A
Morena
Emilia
E
Carraro
Fabio
F
Nico
Beatrice
B
Ribatti
Domenico
D
Presta
Marco
M
D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D053495:Osteopontin; D010766:Phosphorylation; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D016753:Interleukin-10; D048051:p38 Mitogen-Activated Protein Kinases