Cell selective glucocorticoid induction of caveolin-1 and caveolae in differentiating pulmonary alveolar epithelial cell cultures.
Increased caveolin-1 expression is a marker of the differentiation of lung alveolar epithelial type II cells into a type I phenotype. Here, we show in both a primary differentiating rat alveolar culture, and a human alveolar cell line (A549) that caveolae formation and caveolin-1 expression are dependent upon dexamethasone Dex, and is inhibited by the glucocorticoid receptor (GR) antagonist, mifepristone. Study of a panel of 20 different cell types showed the effect of (Dex) upon caveolin-1 expression to be highly cell selective for lung alveolar epithelial cells. The actions of glucocorticoid upon caveolin-1 appear indirect acting via intermediary genes as evidenced by cycloheximide (CHX) abolition of Dex-induced increases in caveolin-1 mRNA and by recombinant transfection studies using the caveolin-1 promoter cloned upstream of a reporter gene. Treatment with actinomycin D (ACD) revealed that the effects of Dex are also, at least in part, mediated by stabilisation of caveolin-1 mRNA. Collectively, these results indicate that glucocorticoids modulate the expression of caveolin-1 and caveolae biogenesis within alveolar epithelial cells via both transcriptional and translational modifications. The cell-selective effects of glucocorticoid upon caveolin may represent a previously unrecognised mechanism by which glucocorticoids affect lung development.
Barar
Jaleh
J
Cardiopulmonary Research, Welsh School of Pharmacy, Cardiff University, Cardiff, UK.
Campbell
Lee
L
Hollins
Andrew J
AJ
Thomas
Nicholas P B
NP
Smith
Mathew W
MW
Morris
Christopher J
CJ
Gumbleton
Mark
M
D000818:Animals; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000096:biosynthesis*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology*; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats
D051242:Caveolin 1; D005938:Glucocorticoids; D003609:Dactinomycin; D003907:Dexamethasone