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Titolo:
High dose of dexamethasone upregulates TCR/CD3-induced calcium response independent of TCR zeta chain expression in human T lymphocytes
Autore:
Nambiar, MP; Enyedy, EJ; Fisher, CU; Warke, VG; Tsokos, GC;
Indirizzi:
Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD 20910 USA Walter Reed Army Inst Res Silver Spring MD USA 20910 Spring, MD 20910 USA Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA Uniformed Serv Univ Hlth Sci Bethesda MD USA 20814 Bethesda, MD 20814 USA
Titolo Testata:
JOURNAL OF CELLULAR BIOCHEMISTRY
fascicolo: 3, volume: 83, anno: 2001,
pagine: 401 - 413
SICI:
0730-2312(2001)83:3<401:HDODUT>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL ANTIGEN-RECEPTOR; LATERAL MOBILITY; MEMBRANE DOMAINS; ACTIVATION; CYTOSKELETON; PHOSPHORYLATION; UBIQUITINATION; CD2; RECOGNITION; STIMULATION;
Keywords:
human T lymphocytes; T cell receptor; T cell signaling; dexamethasone; [Ca2(+)](i) response; TCR zeta chain; lipid rafts;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Tsokos, GC Walter Reed Army Inst Res, Dept Cellular Injury, Bldg 503,Room 1A32,RobertGrant Rd, Silver Spring, MD 20910 USA Walter Reed Army Inst Res Bldg 503,Room 1A32,Robert Grant Rd Silver Spring MD USA 20910
Citazione:
M.P. Nambiar et al., "High dose of dexamethasone upregulates TCR/CD3-induced calcium response independent of TCR zeta chain expression in human T lymphocytes", J CELL BIOC, 83(3), 2001, pp. 401-413

Abstract

Glucocorticoids are very potent anti-inflammatory and immunosuppressive agents that modulate cellular immune responses, although, the molecular mechanisms that impart their complex effects have not been completely defined. We have previously demonstrated that dexamethasone (Dex), a synthetic glucocorticoid, biphasically modulates the expression of TCR (T cell receptor) zeta chain in human T cells. At 10 nM, it induced the expression of TCR zeta chain whereas at 100 nM it inhibited its expression. In parallel to the upregulation of TCR zeta chain, theTCR/CD3-mediaLed [Ca2+](i) response was enhanced in 10 nM Dex-treated cells. However, at 100 nM, Dex treatment enhanced TCR/CD3-mediated [Ca2+](i) response without the induction of TCR zeta chain expression. Because the classical transcriptional model of glucocorticoid action cannot account for the effects of high dose of Dex, here we studied alternative mechanisms of action. We show that, increased and morel sustained TCR/CD3-mediated [Ca2+](i) response was also observed in 100 nM Dex-treated cells in the presence of actinomycin D or cycloheximide suggesting that cellular transcription and/or de novo protein synthesis are not requiredfor the induction. The TCR/CD3-mediated hyper [Ca2+](i) response in 100 nMDex-treated cells was readily reversible by short-term culture in steroid-free medium. RU-486, a competitive antagonist of Dex, inhibited the increase in [Ca2+](i) response suggesting that the effect of Dex is mediated through the glucocorticoid receptor. Although the lipid-raft association of the TCR chain was not significantly increased, high-close of Dex increased the amount of ubiquitinated form of the TCR zeta chain in the cell membrane along with increased levels of actin. Fluorescence microscopy showed that high-dose of Dex alters the distribution of the TCR zeta chain and form more distinct clusters upon TCR/CD3 stimulation. These results suggest that high dose of Dex perturbs the membrane distribution of TCR zeta chain leading to more functional signaling clusters that result in increased TCR/CD3-mediated [Ca2+](i) response independent of TCR zeta chain expression. J. Cell. Biochem. 83: 401-413, 2001. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 22:50:36