Expression of the human glucocorticoid receptor α and β isoforms in human respiratory epithelial cells and their regulation by dexamethasone

Two isoforms of the human glucocorticoid receptor (hGR) have been described, hGR alpha and hGR beta. We analyzed the expression and regulation of both hGR isoforms in human respiratory epithelial cells (BEAS-2B, A549, and primary nasal epithelial cells). In BEAS-2B cells, the expression of hGR alpha messenger RNA (mRNA) was much higher than that of hGR beta mRNA, Dexamethasone (DEX) (10(-6) M) downregulated hGR alpha mRNA at 6 and 24 h (55 +/- 8 and 58 +/- 5% of control, respectively; P < 0.01), whereas it decreased hGR<beta> mRNA only at 6 h (55 +/- 7% of control; P < 0.01), Downregulation of hGR<alpha> and hCRS mRNAs occurred even in the presence of cycloheximide, Actinomycin-D studies revealed that DEX enhanced the stabilization of hGR alpha and hGR beta messages, hGR alpha but not hGR beta protein was detected in BEAS-2B, A549, and nasal epithelial cells. After 24 h of incubation, 10(-6) M DEX decreased the expression of hGR alpha protein in BEAS-2B, A549, and nasal epithelial cells (16 +/- 4, 14 +/- 4 and 28 +/- 7% of control, respectively; P < 0.01), These results suggest that in respiratory epithelial cells: (7) hGR<alpha> is much more expressed than hGR beta at both the mRNA and protein levels; (2) hGR alpha is downregulated by corticosteroids both in cell lines (BEAS-2B, A549) and in nasal primary cells; and (3) transcriptional, post-transcriptional, and post translational mechanisms appear to be involved in the regulation of hGR expression by corticosteroids.