Expression of the human glucocorticoid receptor alpha and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone.

Abstract:

:Two isoforms of the human glucocorticoid receptor (hGR) have been described, hGRalpha and hGRbeta. 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 hGRalpha messenger RNA (mRNA) was much higher than that of hGRbeta mRNA. Dexamethasone (DEX) (10(-6) M) downregulated hGRalpha mRNA at 6 and 24 h (55 +/- 8 and 58 +/- 5% of control, respectively; P < 0.01), whereas it decreased hGRbeta mRNA only at 6 h (55 +/- 7% of control; P < 0.01). Downregulation of hGRalpha and hGRbeta mRNAs occurred even in the presence of cycloheximide. Actinomycin-D studies revealed that DEX enhanced the stabilization of hGRalpha and hGRbeta messages. hGRalpha but not hGRbeta protein was detected in BEAS-2B, A549, and nasal epithelial cells. After 24 h of incubation, 10(-6) M DEX decreased the expression of hGRalpha 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) hGRalpha is much more expressed than hGRbeta at both the mRNA and protein levels; (2) hGRalpha 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.

authors

Pujols L,Mullol J,Pérez M,Roca-Ferrer J,Juan M,Xaubet A,Cidlowski JA,Picado C

doi

10.1165/ajrcmb.24.1.4024

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

49-57

issue

1

eissn

1044-1549

issn

1535-4989

journal_volume

24

pub_type

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