GLUCOCORTICOID HORMONES UP-REGULATE INTERLEUKIN-2 RECEPTOR-ALPHA GENE-EXPRESSION

We present evidence that glucocorticoid hormones increase expression of IL-2Rec α chain on T cells by regulating IL-2Rec α gene transcription. We have previously reported that glucocorticoids can upregulate IL-2Rec α mRNA and protein expression in some T cell hybrids. In the present study we show that the glucocorticoid analogue dexamethasone increases mRNA levels of the endogenous IL-2Rec α gene and the expression of plasmids containing 5′-flanking sequences of the IL-2Rec α gene linked to CAT reporter genes transiently transfected into different cell lines. We show that the dexamethasone effect depends on cis-acting regulatory elements in a segment (-1835/-802) of the mouse gene that also contains cytokine response elements and a inducible DNase I-hypersensitive site. Dexamethasone responses of IL-2Rec α-CAT reporter gene constructs were observed in a CTL line, in an IL-3-dependent bone marrow-derived cell line, and in COS7 monkey kidney cells. In the latter the response depended on cotransfection of a glucocorticoid receptor expression yector. The biological relevance of the glucocorticoid-mediated upregulation of the IL-2Rec α gene is discussed. © 1993 Academic Press. All rights reserved.