Am. J. Respir. Crit. Care Med., Vol 155, No. 3, 03 1997, 1117-1122.
In vitro and in vivo modulation of alpha- and beta-glucocorticoid- receptor mRNA in human bronchial epithelium
SH Korn, EF Wouters, G Wesseling, JW Arends and FB Thunnissen
Department of Pulmonology, University of Limburg, Maastricht, The Netherlands.
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
glucocorticoid- receptor (GR) gene expression. In this study, the effect of
budesonide on alpha- and beta-GR gene expression in human bronchial
epithelial cells was investigated in vitro and in vivo. A bronchial
epithelial 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
downregulation 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 epithelial cells
or alveolar macrophages. The time between the last inhalation and sampling
of cells ranged from 0.5 to 8 h. However, a significant downregulation of
alpha-GR mRNA was observed when the time between the last inhalation and
sampling of cells was more than 2 h. Normalization of the downregulation of
GR mRNA expression in bronchial epithelial cells is explained by the
pharmacokinetics of inhaled budesonide in the human lung.
