Selective regulation of glucocorticoid receptor translational isoforms in T cells and B cells (85.7)

Abstract

Abstract The glucocorticoid receptor (GR) has eight translational isoforms, each of which has a distinct ability to regulate gene expression and to mediate apoptosis. Little is known, however, about whether cell activation or differentiation alters the GR isoforms. We determined the pattern of GR isoform expression in purified human lymphocytes at rest and after activation with mitogens. Stimulation of T cells with ConA led to a slight increase in GR-A and induced a 3-5-fold increase in GR-C. In contrast, activation of B cells with CpG containing DNA did not alter the expression of GR isoforms. To determine the functional consequences of elevated GR-C in activated T cells, we screened the results of microarray studies of Jurkat cells expressing only single GR isoforms to search for genes that were selectively induced by glucocorticoids in cells expressing GR-C but not the other isoforms. We found seven genes that were selectively activated by dexamethasone (DEX) in GR-C-expressing cells and tested the influence of T cell activation on the ability of DEX to activate the expression of these genes. Two of the tested genes, AIM1 and TUBA3E, were significantly increased by DEX only in activated T cells, suggesting that induction of the GR-C isoform had enabled the glucocorticoid to alter the expression of these genes. These results suggest that activation of immune cells can lead to alterations in the expression of GR isoforms that modify the glucocorticoid-induced gene expression.