SEARCH:   Advanced

Blood, 1 September 2008, Vol. 112, No. 5, pp. 1610-1619. Prepublished online as a Blood First Edition Paper on May 29, 2008; DOI 10.1182/blood-2008-01-135111. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-135111v1 112/5/1610    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Kuipers, H. F. Articles by van den Elsen, P. J. PubMed PubMed Citation Articles by Kuipers, H. F. Articles by van den Elsen, P. J. Related Collections Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS CC chemokine receptor 5 gene promoter activation by the cyclic AMP response element binding transcription factor Hedwich F. Kuipers1,2, Paula J. Biesta1, Lisette J. Montagne2, Elise S. van Haastert2, Paul van der Valk2, and Peter J. van den Elsen1,2 1 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden; and 2 Department of Pathology, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands The chemokine receptor CCR5 is implicated in the pathogenesis of various inflammatory diseases, such as multiple sclerosis (MS), atherosclerosis, transplant rejection, and autoimmunity. In previous studies, we have shown that MS lesions are characterized by enhanced expression of transcription factors associated with stress responses, ie, IRF-1, NF-B, and CREB-1, which modulate expression of both classes of major histocompatibility complex (MHC) molecules. The expression of MHC-I and MHC-II molecules greatly overlaps with the expression of CCR5 in MS lesions. Therefore, we investigated whether these factors are also involved in the transcriptional regulation of CCR5. Using in vitro assays, we determined that neither IRF-1 nor NF-B is involved in the activation of the CCR5 promoter. This is corroborated by the finding that these factors are not involved in the induction of endogenous CCR5 transcription in various cell types. In contrast, we show that CCR5 expression is regulated by the cAMP/CREB pathway and that interference in this pathway affects endogenous CCR5 transcription. From this, we conclude that the cAMP/CREB pathway is involved in the regulation of CCR5 transcription and that, given the ubiquitous nature of CREB-1 protein expression, additional regulatory mechanisms must contribute to cell type-specific expression of CCR5. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020