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Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2001, Vol. 97, No. 6, pp. 1611-1617 GENE THERAPY Adenovirus-mediated expression of a mutant IB kinase 2 inhibits the response of endothelial cells to inflammatory stimuli Wolfgang Oitzinger, Renate Hofer-Warbinek, Johannes A. Schmid, Yuri Koshelnick, Bernd R. Binder, and Rainer de Martin From the Department of Vascular Biology and Thrombosis Research, University of Vienna, Vienna, Austria. In a variety of cell types, the transcription factor nuclear factor B (NF-B) functions as a mediator of stress and immune responses. In endothelial cells (ECs), it controls the expression of genes encoding, eg, cytokines, cell adhesion molecules, and procoagulatory proteins. This study investigates the effect of NF-B suppression on several pathophysiologic functions of ECs, including inflammation, coagulation, and angiogenesis. A recombinant adenovirus was generated for expression of a dominant negative (dn) mutant of IB kinase 2 (IKK2), a kinase that acts as an upstream activator of NF-B. dnIKK2 inhibited NF-B, resulting in strongly reduced nuclear translocation and DNA binding activity of the transcription factor and lack of expression of several proinflammatory markers, including E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and interleukin-8. Concomitantly, inhibition of leukocyte binding to dnIKK2-expressing ECs could be demonstrated in a cell adhesion assay. Furthermore, expression of tissue factor as well as the ability to form capillary tubes in a matrigel assay was impaired in dnIKK2-expressing ECs. These data demonstrate that NF-B is of central importance not only for the inflammatory response but also for a number of other EC functions. Therefore, this transcription factor as well as its upstream regulatory signaling molecules may represent favorable targets for therapeutic interference. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Chavey, M. Muhlbauer, C. Bossard, A. Freund, S. Durand, C. Jorgensen, C. Jobin, and G. Lazennec Interleukin-8 Expression Is Regulated by Histone Deacetylases through the Nuclear Factor-{kappa}B Pathway in Breast Cancer Mol. Pharmacol., November 1, 2008; 74(5): 1359 - 1366. [Abstract] [Full Text] [PDF] K. M. Stuhlmeier Hyaluronan Production in Synoviocytes as a Consequence of Viral Infections: HAS1 ACTIVATION BY EPSTEIN-BARR VIRUS AND SYNTHETIC DOUBLE- AND SINGLE-STRANDED VIRAL RNA ANALOGS J. Biol. 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