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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3642-3646. Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-03-0817. This Article Full Text (PDF) All Versions of this Article: 2004-03-0817v1 104/12/3642    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 Pluvinet, R. Articles by Aran, J. M Search for Related Content PubMed PubMed Citation Articles by Pluvinet, R. Articles by Aran, J. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 3, 2004 Accepted May 14, 2004 RNAi-mediated silencing of CD40 prevents leukocyte adhesion on CD154-activated endothelial cells Raquel Pluvinet, Jordi Petriz, Joan Torras, Inmaculada Herrero-Fresneda, Josep M Cruzado, Josep M Grinyo, and Josep M Aran* Medical and Molecular Genetics Center, Institut de Recerca Oncologica (IRO), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain Servei d'Hemoterapia i Hemostasia, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Universitat de Barcelona, Barcelona, Spain Laboratory of Nephrology, Medicine Department, Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de llobregat, Barcelona, Spain * Corresponding author; email: jaran{at}iro.es. The CD40-CD154 dyad has a central role in the development of immune-inflammatory processes. Therefore, disruption of CD40 signaling has the potential to be therapeutically useful in a number of disease indications including autoimmune syndromes, atherosclerosis and allograft rejection. Blocking antibodies to CD154 have been successfully employed in experimental animal models, and recently in clinical trials, to prevent or treat these immunologically induced diseases. However, the thrombotic events observed in some of the above studies raise important issues regarding future use of anti-CD154 antibodies in humans. In this study we demonstrate that a small interfering RNA (siRNA) can effectively reduce the surface expression of the human CD40 co-stimulatory receptor. Moreover, by rendering endothelial cells unresponsive to CD154+ Jurkat cell-mediated activation through RNA interference, induction of endothelial cell-adhesion molecule expression and leukocyte adhesion is prevented in vitro. Thus, anti-CD40 siRNA may become a safe and effective therapeutic option for interfering with CD40-CD154-mediated acute or chronic immune-inflammatory conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Pluvinet, R. Olivar, J. Krupinski, I. Herrero-Fresneda, A. Luque, J. Torras, J. M. Cruzado, J. M. Grinyo, L. Sumoy, and J. M. Aran CD40: an upstream master switch for endothelial cell activation uncovered by RNAi-coupled transcriptional profiling Blood, November 1, 2008; 112(9): 3624 - 3637. [Abstract] [Full Text] [PDF] K.-G. Shyu, B.-W. Wang, P. Kuan, and H. Chang RNA Interference for Discoidin Domain Receptor 2 Attenuates Neointimal Formation in Balloon Injured Rat Carotid Artery Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1447 - 1453. [Abstract] [Full Text] [PDF] M. Suzuki, X. Zheng, X. Zhang, M. Li, C. Vladau, T. E. Ichim, H. Sun, L. R. Min, B. Garcia, and W.-P. Min Novel Vaccination for Allergy through Gene Silencing of CD40 Using Small Interfering RNA J. Immunol., June 15, 2008; 180(12): 8461 - 8469. [Abstract] [Full Text] [PDF] T. Korff, K. Aufgebauer, and M. Hecker Cyclic Stretch Controls the Expression of CD40 in Endothelial Cells by Changing Their Transforming Growth Factor-{beta}1 Response Circulation, November 13, 2007; 116(20): 2288 - 2297. [Abstract] [Full Text] [PDF] E. Sitati, E. E. McCandless, R. S. Klein, and M. S. Diamond CD40-CD40 Ligand Interactions Promote Trafficking of CD8+ T Cells into the Brain and Protection against West Nile Virus Encephalitis J. Virol., September 15, 2007; 81(18): 9801 - 9811. [Abstract] [Full Text] [PDF] P. Geraldes, S. Gagnon, S. Hadjadj, Y. Merhi, M. G. Sirois, I. Cloutier, and J.-F. Tanguay Estradiol blocks the induction of CD40 and CD40L expression on endothelial cells and prevents neutrophil adhesion: An ER{alpha}-mediated pathway Cardiovasc Res, August 1, 2006; 71(3): 566 - 573. [Abstract] [Full Text] [PDF] B. Davis and M.-H. Zou CD40 Ligand-Dependent Tyrosine Nitration of Prostacyclin Synthase In Vivo Circulation, October 4, 2005; 112(14): 2184 - 2192. [Abstract] [Full Text] [PDF] C. A. Sledz and B. R. G. Williams RNA interference in biology and disease Blood, August 1, 2005; 106(3): 787 - 794. [Abstract] [Full Text] [PDF]

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