Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappaB.
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)
Ayroldi
E
E
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Via del Giochetto, 06100 Perugia, Italy.
Migliorati
G
G
Bruscoli
S
S
Marchetti
C
C
Zollo
O
O
Cannarile
L
L
D'Adamio
F
F
Riccardi
C
C
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D016350:Leucine Zippers / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D007376:Interleukin-2; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C404226:TSC22D3 protein, human; D014157:Transcription Factors; D003907:Dexamethasone