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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2003-01-0288. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0288v1 102/5/1740    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pollet, I. Articles by Karsan, A. Search for Related Content PubMed PubMed Citation Articles by Pollet, I. Articles by Karsan, A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2003, Vol. 102, No. 5, pp. 1740-1742 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Bacterial lipopolysaccharide directly induces angiogenesis through TRAF6-mediated activation of NF-B and c-Jun N-terminal kinase Ingrid Pollet, Christy J. Opina, Carla Zimmerman, Kevin G. Leong, Fred Wong, and Aly Karsan From the Department of Medical Biophysics, British Columbia Cancer Agency; Department of Pathology and Laboratory Medicine, University of British Columbia; Experimental Medicine Program, University of British Columbia; and Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada. The intracellular pathways by which inflammatory mediators transmit their angiogenic signals is not well studied. The effects of a potent inflammatory mediator, bacterial lipopolysaccharide (LPS), are transmitted through Toll-like receptors (TLRs). A major, although not exclusive, LPS/TLR intracellular signaling pathway is routed through TNF (tumor necrosis factor) receptor associated factor 6 (TRAF6). In this report we demonstrate that LPS directly stimulates endothelial sprouting in vitro. By blocking TRAF6 activity using retroviral expression of a dominant-negative TRAF6 in endothelial cells, we show that TRAF6 is absolutely required for the LPS-initiated angiogenic response in vitro and in vivo. Inhibition of either c-Jun N-terminal kinase (JNK) activity or nuclear factor B (NF-B) activity, downstream of TRAF6, is sufficient to inhibit LPS-induced endothelial sprouting. In contrast, only inhibition of NF-B, but not JNK, activity blocks basic fibroblast growth factor (bFGF)–induced angiogenesis. Our findings thus demonstrate a direct endothelial-stimulatory role of LPS in initiating angiogenesis through activation of TRAF6-dependent signaling pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Sethi, B. Sung, and B. B. Aggarwal Nuclear Factor-{kappa}B Activation: From Bench to Bedside Experimental Biology and Medicine, January 1, 2008; 233(1): 21 - 31. [Abstract] [Full Text] [PDF] L. Macedo, G. Pinhal-Enfield, V. Alshits, G. Elson, B. N. Cronstein, and S. J. Leibovich Wound Healing Is Impaired in MyD88-Deficient Mice: A Role for MyD88 in the Regulation of Wound Healing by Adenosine A2A Receptors Am. J. Pathol., December 1, 2007; 171(6): 1774 - 1788. [Abstract] [Full Text] [PDF] R. Zhande, S. M. Dauphinee, J. A. Thomas, M. Yamamoto, S. Akira, and A. 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