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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4145-4154. Prepublished online as a Blood First Edition Paper on February 5, 2008; DOI 10.1182/blood-2007-08-110338. This Article Full Text Full Text (PDF) Supplemental Methods, Table, and Figures Erratum (v111,p5761) All Versions of this Article: blood-2007-08-110338v1 111/8/4145    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Abdel-Malak, N. A. Articles by Hussain, S. N. A. PubMed PubMed Citation Articles by Abdel-Malak, N. A. Articles by Hussain, S. N. A. Related Collections Chemokines, Cytokines, and Interleukins Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Angiopoietin-1 promotes endothelial cell proliferation and migration through AP-1–dependent autocrine production of interleukin-8 Nelly A. Abdel-Malak1, Coimbatore B. Srikant2, Arnold S. Kristof1, Sheldon A. Magder1, John A. Di Battista3, and Sabah N. A. Hussain1 1 Critical Care and Respiratory Divisions and Meakins-Christie Laboratories 2 Division of Endocrinology, and 3 Division of Rheumatology, Department of Medicine, McGill University Health Centre, McGill University, Montreal, QC Angiopoietin-1 (Ang-1), ligand for the endothelial cell–specific Tie-2 receptors, promotes migration and proliferation of endothelial cells, however, whether these effects are promoted through the release of a secondary mediator remains unclear. In this study, we assessed whether Ang-1 promotes endothelial cell migration and proliferation through the release of interleukin-8 (IL-8). Ang-1 elicited in human umbilical vein endothelial cells (HUVECs) a dose- and time-dependent increase in IL-8 production as a result of induction of mRNA and enhanced mRNA stability of IL-8 transcripts. IL-8 production is also elevated in HUVECs transduced with retroviruses expressing Ang-1. Neutralization of IL-8 in these cells with a specific antibody significantly attenuated proliferation and migration and induced caspase-3 activation. Exposure to Ang-1 triggered a significant increase in DNA binding of activator protein-1 (AP-1) to a relatively short fragment of IL-8 promoter. Upstream from the AP-1 complex, up-regulation of IL-8 transcription by Ang-1 was mediated through the Erk1/2, SAPK/JNK, and PI-3 kinase pathways, which triggered c-Jun phosphorylation on Ser63 and Ser73. These results suggest that promotion of endothelial migration and proliferation by Ang-1 is mediated, in part, through the production of IL-8, which acts in an autocrine fashion to suppress apoptosis and facilitate cell proliferation and migration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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