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Blood, 1 February 2004, Vol. 103, No. 3, pp. 1124-1130. Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-07-2427. This Article Full Text (PDF) All Versions of this Article: 2003-07-2427v1 103/3/1124    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 Blouin, C. C Articles by Richard, D. E Search for Related Content PubMed PubMed Citation Articles by Blouin, C. C Articles by Richard, D. E Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted July 17, 2003 Accepted September 29, 2003 Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor-1 Caroline C Blouin, Elisabeth L Page, Guylaine M Soucy, and Darren E Richard* Centre de Recherche de L'Hotel-Dieu de Quebec, Quebec, PQ, Canada; Department of Medicine, Universite Laval, Quebec, PQ, Canada * Corresponding author; email: darren.richard{at}crhdq.ulaval.ca. Hypoxia-inducible factor-1 (HIF-1) regulates many genes induced by low oxygen conditions. The expression of important hypoxic genes such as glucose transporter-1 and vascular endothelial growth factor are increased in macrophages during wound healing and in the presence of the endotoxin, lipopolysaccaride (LPS). Recent studies have demonstrated that non-hypoxic stimuli can also activate HIF-1 in a cell specific manner. Here, we demonstrate that in macrophages, LPS can control the activation of hypoxia-regulated genes through the HIF-1 pathway. We show that in these cells, protein expression levels of HIF-1 are strongly increased to levels comparable to hypoxic induction. HIF-1 mRNA levels are markedly increased following LPS stimulation, suggesting a transcriptional induction. In functional studies, the LPS-induced HIF-1 complex could specifically bind to the HIF-1 DNA binding motif. Additionally, when cells were transfected with a HIF-1 specific reporter construct, LPS could strongly activate the expression of the reporter to levels that surpassed those observed after hypoxic induction. This induction was blocked by the co-transfection of a dominant-negative form of HIF-1. These results indicate that the HIF-1 complex is involved in macrophage gene activation following LPS exposure and identify a novel pathway that could play a determinant role during inflammation and wound healing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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