Ayroldi E, Migliorati G, Bruscoli S, Marchetti C, Zollo O, Cannarile L, D'Adamio F, Riccardi C
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Via del Giochetto, 06100 Perugia, Italy.
Blood. 2001 Aug 1;98(3):743-53. doi: 10.1182/blood.v98.3.743.
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)
此前已鉴定出一种编码糖皮质激素诱导亮氨酸拉链（GILZ）的新基因，其表达受地塞米松上调。本研究分析了GILZ在T细胞活化控制中的作用及其与核因子κB（NF-κB）的可能相互作用。结果表明，GILZ抑制T细胞受体（TCR）诱导的白细胞介素-2/白细胞介素-2受体表达和NF-κB活性。特别是，由于GILZ与NF-κB亚基的直接蛋白质-蛋白质相互作用，GILZ抑制NF-κB核转位和DNA结合。此外，GILZ介导的TCR诱导反应调节是一个回路的一部分，因为TCR触发会下调GILZ表达。这些结果确定了一种参与地塞米松诱导的NF-κB活性调节和T细胞活化的新分子机制。（《血液》。2001年；98:743-753）
