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Blood, 1 August 2001, Vol. 98, No. 3, pp. 743-753

IMMUNOBIOLOGY

Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappa B

Emira Ayroldi, Graziella Migliorati, Stefano Bruscoli, Cristina Marchetti, Ornella Zollo, Lorenza Cannarile, Francesca D'Adamio, and Carlo Riccardi

From the Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Italy.

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 kappa B (NF-kappa B). Results indicate that GILZ inhibits both T-cell receptor (TCR)-induced interleukin-2/interleukin-2 receptor expression and NF-kappa B activity. In particular, GILZ inhibits NF-kappa B nuclear translocation and DNA binding due to a direct protein-to-protein interaction of GILZ with the NF-kappa B 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-kappa B activity and T-cell activation.

© 2001 by The American Society of Hematology.
 

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