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

Previously a novel gene was identified that encodes a glucocorticoid-induce d leucine zipper (GILZ) whose expression is up-regulated by dexamethasone. This study analyzed the role of GILZ in the control of T-cell activation an d 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 dire ct protein-to-protein interaction of GILZ with the NF-kappaB subunits. More over, GILZ-mediated modulation of TCR-induced responses is part of a circui t because TCR triggering down-regulates GILZ expression. These results iden tify a new molecular mechanism involved in the dexamethasone-induced regula tion of NF-kappaB activity and T-cell activation. (C) 2001 by The American Society of Hematology.