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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4520-4526. Prepublished online as a Blood First Edition Paper on March 2, 2004; DOI 10.1182/blood-2003-06-2118. This Article Full Text (PDF) All Versions of this Article: 2003-06-2118v1 103/12/4520    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 Wong, F. Articles by Karsan, A. Search for Related Content PubMed PubMed Citation Articles by Wong, F. Articles by Karsan, A. Social Bookmarking                   What's this? Submitted June 26, 2003 Accepted February 7, 2004 Lipopolysaccharide initiates a TRAF6-mediated endothelial survival signal Fred Wong, Christopher Hull, Rachel Zhande, Jennifer Law, and Aly Karsan* Medical Biophysics, British Columbia Cancer Agency, Vancouver, BC, Canada; Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, BC, Canada; Medical Biophysics, British Columbia Cancer Agency, Vancouver, BC, Canada; Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada * Corresponding author; email: akarsan{at}bccrc.ca. Similar to tumor necrosis factor (TNF), bacterial lipopolysaccharide (LPS) elicits parallel apoptotic and anti-apoptotic pathways in endothelial cells. The overall result is that there is minimal endothelial cell death in response to LPS without inhibition of the cytoprotective pathway. While the TNF-induced death and survival pathways have been relatively well elucidated, much remains to be learned about LPS signaling events in this regard. It is known that the transcription factor NF-B provides a critical cell survival signal in response to TNF, but is not an essential component of the LPS-induced survival pathway. The TNF receptor-associated factor (TRAF)6 is a major effector of multiple LPS-induced signals, including a c-Jun N-terminal kinase (JNK)-mediated apoptotic response. In this report we demonstrate that following LPS stimulation, TRAF6 also transmits an important endothelial cell survival signal in a situation of complete NF-B blockade. In response to LPS, TRAF6 activates the phosphatidylinositol 3'-kinase (PI3K)/Akt pathway, but not ERK1/2 mitogen-activated protein kinases (MAPK) in endothelial cells. Activation of PI3K signals a critical anti-apoptotic pathway in response to LPS in endothelial cells, whereas ERK1/2 do not. Thus TRAF6 acts as a bifurcation point of the LPS-initiated death and survival signals in endothelial cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-S. Choi, H.-J. Choi, J.-K. Min, B.-J. Pyun, Y.-S. Maeng, H. Park, J. Kim, Y.-M. Kim, and Y.-G. Kwon Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production Blood, October 1, 2009; 114(14): 3117 - 3126. [Abstract] [Full Text] [PDF] H. Karahashi, K. S. Michelsen, and M. Arditi Lipopolysaccharide-Induced Apoptosis in Transformed Bovine Brain Endothelial Cells and Human Dermal Microvessel Endothelial Cells: The Role of JNK J. Immunol., June 1, 2009; 182(11): 7280 - 7286. [Abstract] [Full Text] [PDF] D. McClenahan, K. Hellenbrand, D. Atapattu, N. Aulik, D. Carlton, A. Kapur, and C. Czuprynski Effects of Lipopolysaccharide and Mannheimia haemolytica Leukotoxin on Bovine Lung Microvascular Endothelial Cells and Alveolar Epithelial Cells Clin. Vaccine Immunol., February 1, 2008; 15(2): 338 - 347. [Abstract] [Full Text] [PDF] R. Zhande, S. M. Dauphinee, J. A. Thomas, M. Yamamoto, S. Akira, and A. Karsan FADD Negatively Regulates Lipopolysaccharide Signaling by Impairing Interleukin-1 Receptor-Associated Kinase 1-MyD88 Interaction Mol. Cell. Biol., November 1, 2007; 27(21): 7394 - 7404. [Abstract] [Full Text] [PDF] S. T. Qureshi, X. Zhang, E. Aberg, N. Bousette, A. Giaid, P. Shan, R. M. Medzhitov, and P. J. Lee Inducible Activation of TLR4 Confers Resistance to Hyperoxia-Induced Pulmonary Apoptosis. J. Immunol., April 15, 2006; 176(8): 4950 - 4958. [Abstract] [Full Text] [PDF] W. Chao, Y. Shen, X. Zhu, H. Zhao, M. Novikov, U. Schmidt, and A. Rosenzweig Lipopolysaccharide Improves Cardiomyocyte Survival and Function after Serum Deprivation J. Biol. Chem., June 10, 2005; 280(23): 21997 - 22005. [Abstract] [Full Text] [PDF]

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