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Cutting Edge: IL-1 Mediates the Proangiogenic Activity of Osteopontin-Activated Human Monocytes¹

Antonella Naldini^2,*, Daria Leali, Annalisa Pucci^*, Emilia Morena^*, Fabio Carraro^*, Beatrice Nico, Domenico Ribatti and Marco Presta

^* Unit of Neuroimmunophysiology, Department of Physiology, University of Siena, Siena, Italy; Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy; and Department of Human Anatomy and Histology, University of Bari, Bari, Italy

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-1 up-regulation in human monocytes. This was accompanied by the enhanced production of TNF-, 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-1 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-1.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from MIUR (Cofin 2004) and Fondazione MPS (to A.N.) and from MIUR (Centro di Eccellenza IDET, FIRB 2001, Cofin 2004), Fondazione G. Berlucchi, Istituto Superiore Sanità (Progetto Oncotecnologico), and Associazione Italiana per la Ricerca sul Cancro (Italy) (to M.P.).

² Address correspondence and reprint requests to Dr. Antonella Naldini, Unit of Neuroimmunophysiology, Department of Physiology, University of Siena, Via Aldo Moro, 53100 Siena, Italy. E-mail address: Naldini{at}Unisi.it

³ Abbreviations used in this paper: OPN, osteopontin; FGF-2, fibroblast growth factor-2; CM, conditioned medium; CAM, chorioallantoic membrane; qRT-PCR, quantitative RT-PCR; RGD, Arg-Gly-Asp.

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