Year: 2007
Type: article
Abstract: 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 alpha (GCR alpha) 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 alpha nuclear translocation and no significant difference in GCR alpha and GCR beta 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.
Source: Blood
Institutions: University of Colorado Denver, National Jewish Health
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: G1195514610, G1222176821, G2037600495, G2533696587, G2562400020, G2632995711, General Clinical Research Center, G3692366001, ATOPIC DERMATITIS & VACCINIA IMMUNIZATION NETWORK: ANIMAL STUDIES CONSORTIUM, Atopic Dermatitis and Vaccinia Immunization Network Clinical Consortium, G608136060, G6083313123, G6494120516, G6890543924, PATHOGENESIS AND ETIOLOGY OF KAWASAKI SYNDROME.
OpenAlex ID: W2018837147