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Blood, 1 January 2009, Vol. 113, No. 1, pp. 224-232. Prepublished online as a Blood First Edition Paper on September 23, 2008; DOI 10.1182/blood-2008-06-165746. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-165746v1 113/1/224    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 Eltzschig, H. K. Articles by Colgan, S. P. Search for Related Content PubMed PubMed Citation Articles by Eltzschig, H. K. Articles by Colgan, S. P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 26, 2008 Accepted August 30, 2008 Central role of Sp1-regulated CD39 in hypoxia / ischemia protection Holger K. Eltzschig*, David Kohler, Tobias Eckle, Tianqing Kong, Simon C. Robson, and Sean P. Colgan Department of Anesthesiology and Perioperative Medicine, University of Colorado Health Sciences Center, Denver, CO, United States Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tubingen, Germany Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States Gastroenterology Division, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA, United States Mucosal Inflammation Program, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, United States * Corresponding author; email: holger.eltzschig{at}uchsc.edu. Hypoxia is common to a number of inflammatory diseases, where multiple cell types release adenine-nucleotides (particularly ATP/ADP). ATP/ADP is metabolized to adenosine through a two-step enzymatic reaction initiated by CD39 (ecto-nucleoside-triphosphate-diphosphohydrolase-1). Thus, extracellular adenosine becomes available to regulate multiple inflammatory endpoints. Here, we hypothesized that hypoxia transcriptionally upregulates CD39 expression. Initial studies revealed hypoxia-dependent increases in CD39-mRNA and immunoreactivity on endothelia. Examination of the human CD39 gene-promoter identified a region important in hypoxia-inducibility. Multiple levels of analysis, including site-directed mutagenesis, chromatin-immunoprecipitation and inhibition by antisense revealed a critical role for transcription-factor Sp1 in hypoxia-induction of CD39. Using a combination of cd39-/--mice and Sp1 siRNA in in vivo cardiac ischemia models revealed Sp1-mediated induction of cardiac CD39 during myocardial ischemia. In summary, these results identify a novel Sp1-dependent regulatory pathway for CD39 and indicate the likelihood that CD39 is central to protective responses to hypoxia / ischemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. P. Hilchey, J. J. Kobie, M. R. Cochran, S. Secor-Socha, J.-C. E. Wang, O. Hyrien, W. R. Burack, T. R. Mosmann, S. A. Quataert, and S. H. Bernstein Human Follicular Lymphoma CD39+-Infiltrating T Cells Contribute to Adenosine-Mediated T Cell Hyporesponsiveness J. Immunol., November 15, 2009; 183(10): 6157 - 6166. [Abstract] [Full Text] [PDF] T. Eckle, M. Koeppen, and H. K. Eltzschig Role of Extracellular Adenosine in Acute Lung Injury Physiology, October 1, 2009; 24(5): 298 - 306. [Abstract] [Full Text] [PDF] X. Sun, A. Cardenas, Y. Wu, K. Enjyoji, and S. C. Robson Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice Am J Physiol Gastrointest Liver Physiol, August 1, 2009; 297(2): G306 - G311. [Abstract] [Full Text] [PDF]

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