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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 (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 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. Social Bookmarking                   What's this? Submitted January 29, 2003 Accepted April 11, 2003 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* Department of Medical Biophysics, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Experimental Medicine Program, University of British Columbia, Vancouver, BC, Canada Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada * Corresponding author; email: akarsan{at}bccancer.bc.ca. 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 (TLR). A major, though not exclusive, LPS/TLR intracellular signaling pathway is routed through TNF receptor associated factor (TRAF)6. 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 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? 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