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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 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 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 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. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY ATF2 impairs glucocorticoid receptor–mediated transactivation in human CD8+ T cells Ling-bo Li1, Donald Y. M. Leung1,4, Matthew J. Strand2,3, and Elena Goleva1 Divisions of1 Pediatric Allergy and Immunology and 2 Biostatistics, National Jewish Medical and Research Center, Denver, CO; 3 Section of Biostatistics and Informatics and 4 Department of Pediatrics, University of Colorado and Health Sciences Center, Denver Chronic inflammatory diseases often have residual CD8+ T-cell infiltration despite treatment with systemic corticosteroids, which suggests divergent steroid responses between CD4+ and CD8+ cells. To examine steroid sensitivity, dexamethasone (DEX)–induced histone H4 lysine 5 (K5) acetylation and glucocorticoid receptor (GCR) translocation were evaluated. DEX treatment for 6 hours significantly induced histone H4 K5 acetylation in normal CD4+ cells (P = .001) but not in CD8+ cells. DEX responses were functionally impaired in CD8+ compared with CD4+ cells when using mitogen-activated protein kinase phosphatase (1 hour; P = .02) and interleukin 10 mRNA (24 hours; P = .004) induction as a readout of steroid-induced transactivation. Normal DEX-induced GCR nuclear translocation and no significant difference in GCR and GCRß mRNA expression were observed in both T-cell types. In addition, no significant difference in SRC-1, p300, or TIP60 expression was found. However, activating transcription factor-2 (ATF2) expression was significantly lower in CD8+ compared with CD4+ cells (P = .009). Importantly, inhibition of ATF2 expression by small interfering RNA in CD4+ cells resulted in inhibition of DEX-induced transactivation in CD4+ cells. The data indicate refractory steroid-induced transactivation but similar steroid-induced transrepression of CD8+ cells compared with CD4+ cells caused by 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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