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Blood, 15 January 2009, Vol. 113, No. 3, pp. 575-584. Prepublished online as a Blood First Edition Paper on October 7, 2008; DOI 10.1182/blood-2008-04-151803. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-04-151803v1 113/3/575    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 Ghosh, M. C Articles by Taub, D. D. Search for Related Content PubMed PubMed Citation Articles by Ghosh, M. C Articles by Taub, D. D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 16, 2008 Accepted September 16, 2008 Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck Manik C Ghosh, Dolgor Baatar, Gary Collins, Arnell Carter, Fred Indig, Arya Biragyn, and Dennis D. Taub* Laboratory of Immunology, Intramural Research Program, National Institute of Aging, National Institute of Health, Baltimore, MD, United States Research Resources Branch, Intramural Research Program, National Institute of Aging, National Institute of Health, Baltimore, MD, United States * Corresponding author; email: taubd{at}grc.nia.nih.gov. Dexamethasone (DM) is a synthetic member of the glucocorticoid (GC) class of hormones that possesses anti-inflammatory and immunosuppressant activity and is commonly utilized to treat chronic inflammatory disorders, severe allergies and other disease states. While GC are known to mediate well-defined transcriptional effects via GC receptors (GCR), there is increasing evidence that GC also initiate rapid non-genomic signaling events in a variety of cell types. Here, we report that DM induces the phosphorylation of Lck and the activation of other down stream mediators including p59Fyn, Zap70, Rac1 and Vav in resting but not activated human T cells. DM treatment also augments CXCL12-mediated signaling in resting T cells through its cell surface receptor, CXCR4 resulting in the enhanced actin polymerization, Rac activation and cell migration upon ligand exposure. Lck was found to be a critical intermediate in these DM-induced signaling activities. Moreover, DM-mediated Lck phosphorylation in T cells was dependent on the presence of both the GCR and the CD45 molecule. Overall, these results elucidate additional non-genomic effects of DM and the GCR on resting human T cells, inducing Lck and downstream kinase activation and augmenting chemokine signaling and function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Dimitrov, C. Benedict, D. Heutling, J. Westermann, J. Born, and T. Lange Cortisol and epinephrine control opposing circadian rhythms in T cell subsets Blood, May 21, 2009; 113(21): 5134 - 5143. [Abstract] [Full Text] [PDF]

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