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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1570-1577. Prepublished online as a Blood First Edition Paper on May 24, 2007; DOI 10.1182/blood-2007-01-070755. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-070755v1 110/5/1570    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 Li, L.-b. Articles by Goleva, E. Search for Related Content PubMed PubMed Citation Articles by Li, L.-b. Articles by Goleva, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 29, 2007 Accepted May 16, 2007 ATF2 impairs glucocorticoid receptor-mediated transactivation in human CD8+ T cells Ling-bo Li, Donald Y.M. Leung, Matthew J Strand, and Elena Goleva* Division of Pediatric Allergy & Immunology, National Jewish Medical and Research Center, Denver, CO, United States Dept of Pediatrics, University of Colorado at Denver and Health Sciences Center, Denver, CO, United States Div of Biostatistics, Nat'l Jewish Medical & Research Center, & Section of Biostatistics & Informatics, University of Colorado at Denver & Health Sciences Center, Denver, CO * Corresponding author; email: golevae{at}njc.org. Chronic inflammatory diseases often have residual CD8+ T cell infiltration despite treatment with systemic corticosteroids suggesting divergent steroid responses between CD4+ vs. CD8+ cells. To examine steroid sensitivity, dexamethasone (DEX)-induced histone H4 lysine (K)5 acetylation and glucocorticoid receptor (GCR) translocation were evaluated. DEX treatment for 6h significantly induced H4 K5 acetylation in normal CD4+ cells (p=0.001), but not in CD8+ cells. DEX responses were functionally impaired in CD8+ as compared to CD4+ cells, using MKP-1 (1h) (p=0.02) and IL-10 mRNA (24h) (p=0.004) induction as a read-out of steroid-induced transactivation. Normal DEX-induced GCR nuclear translocation and no significant difference in GCR and GCR mRNA expression were observed in both T cell types. Also, no significant difference in SRC-1, p300 and TIP60 expression was found. However, ATF2 expression was significantly lower in CD8+ compared to CD4+ cells (p=0.009). Importantly, inhibition of ATF2 expression by siRNA in CD4+ cells resulted in inhibition of DEX-induced transactivation in CD4+ cells. The data indicates refractory steroid-induced transactivation but similar steroid-induced transrepression of CD8+ cells as compared to CD4+ cells due to decreased levels of the histone acetyltransferase ATF2. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. D. Sloan and K. R. Jerome Herpes Simplex Virus Remodels T-Cell Receptor Signaling, Resulting in p38-Dependent Selective Synthesis of Interleukin-10 J. Virol., November 15, 2007; 81(22): 12504 - 12514. [Abstract] [Full Text] [PDF]

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