IN-VITRO AND IN-VIVO MODULATION OF ALPHA-GLUCOCORTICOID-RECEPTOR AND BETA-GLUCOCORTICOID-RECEPTOR MESSENGER-RNA IN HUMAN BRONCHIAL EPITHELIUM

Despite the central role bronchial epithelial cells play in asthmatic reactions, and the widespread use of inhaled corticosteroids in asthma , no information is available on the effect of glucocorticoids on gluc ocorticoid- receptor (GR) gene expression. In this study, the effect o f budesonide on alpha- and beta-GR gene expression in human bronchial epithelial cells was investigated in vitro and in vivo. A bronchial ep ithelial cell line was exposed in vitro to budesonide, and a dose- and time-dependent synchronous downregulation of alpha- and beta-GR mRNA was observed. A 1-h exposure resulted in a reversible and reduced down regulation as compared with continuous exposure. In healthy volunteers (n = 10), no difference on average was present in GR mRNA expression before or after 4 wk of budesonide inhalation in either bronchial epit helial cells or alveolar macrophages. The time between the last inhala tion and sampling of cells ranged from 0.5 to 8 h. However, a signific ant downregulation of alpha-GR mRNA was observed when the time between the last inhalation and sampling of cells was more than 2 h. Normaliz ation of the downregulation of GR mRNA expression in bronchial epithel ial cells is explained by the pharmacokinetics of inhaled budesonide i n the human lung.