Abstract
Previously a novel gene was identified that encodes a glucocorticoid-induced leucine zipper (GILZ) whose expression is up-regulated by dexamethasone. This study analyzed the role of GILZ in the control of T-cell activation and its possible interaction with nuclear factor kappaB (NF-kappaB). Results indicate that GILZ inhibits both T-cell receptor (TCR)-induced interleukin-2/interleukin-2 receptor expression and NF-kappaB activity. In particular, GILZ inhibits NF-kappaB nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappaB subunits. Moreover, GILZ-mediated modulation of TCR-induced responses is part of a circuit because TCR triggering down-regulates GILZ expression. These results identify a new molecular mechanism involved in the dexamethasone-induced regulation of NF-kappaB activity and T-cell activation. (Blood. 2001;98:743-753)
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Apoptosis / drug effects
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Dexamethasone / pharmacology
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Gene Expression Regulation / drug effects
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Glucocorticoids / chemistry
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Glucocorticoids / immunology
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Glucocorticoids / pharmacology*
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Humans
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Interleukin-2 / metabolism
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Leucine Zippers / drug effects*
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Leucine Zippers / immunology
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Lymphocyte Activation / drug effects*
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / immunology
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Receptors, Interleukin-2 / metabolism
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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Transcription Factors / immunology
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Transcription Factors / pharmacology*
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Tumor Cells, Cultured
Substances
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Glucocorticoids
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Interleukin-2
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NF-kappa B
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2
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TSC22D3 protein, human
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Transcription Factors
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Dexamethasone