Am. J. Respir. Cell Mol. Biol., Volume 24, Number 1, January, 2001 49-57

Expression of the Human Glucocorticoid Receptor  and  Isoforms in Human Respiratory Epithelial Cells and Their Regulation by Dexamethasone

Laura Pujols, Joaquim Mullol, Maria Pérez, Jordi Roca-Ferrer, Manel Juan, Antoni Xaubet, John A. Cidlowski, and César Picado

Institut d'Investigacions Biomèdiques August Pi i Sunyer, Institut Clínic de Pneumologia i Cirurgia Toràcica and Servei d'Otorinolaringologia, Hospital Clínic; Departament d'Immunologia, Hospital Germans Trias i Pujol de Badalona, Barcelona, Catalonia, Spain; and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina

Two isoforms of the human glucocorticoid receptor (hGR) have been described, hGR and hGR. 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 messenger RNA (mRNA) was much higher than that of hGR mRNA. Dexamethasone (DEX) (10⁶ M) downregulated hGR mRNA at 6 and 24 h (55 ± 8 and 58 ± 5% of control, respectively; P < 0.01), whereas it decreased hGR mRNA only at 6 h (55 ± 7% of control; P < 0.01). Downregulation of hGR and hGR mRNAs occurred even in the presence of cycloheximide. Actinomycin-D studies revealed that DEX enhanced the stabilization of hGR and hGR messages. hGR but not hGR protein was detected in BEAS-2B, A549, and nasal epithelial cells. After 24 h of incubation, 10⁶ M DEX decreased the expression of hGR 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: (1) hGR is much more expressed than hGR at both the mRNA and protein levels; (2) hGR 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.

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