Abstract
Rationale: Inhaled corticosteroids (ICS) reduce inflammatory gene expression. This is usually attributed to direct inhibition of inflammatory gene transcription by the glucocorticoid receptor. However, while corticosteroids induce anti-inflammatory gene expression in vitro, this has not been examined in asthmatic subjects taking ICS.
Methods: Bronchial biopsies from atopic asthmatics taking inhaled budesonide (2×200 μg, twice daily for 11 days) or placebo were subjected to gene expression analysis using real-time reverse transcriptase-polymerase chain reaction. mRNA expression for the corticosteroid-inducible genes; TSC22D3 (GILZ), DUSP1 (MKP-1), both anti-inflammatory effectors, and FKBP5 (FKBP51), a regulator of glucocorticoid receptor function, was assessed. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.
Results: Expression of GILZ and FKBP51 were significantly elevated in budesonide-treated subjects compared to placebo. Budesonide also increased GILZ expression in cultured epithelial and smooth muscle cells and immunostaining showed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.
Conclusions: Expression of corticosteroid-induced genes, including the anti-inflammatory gene, GILZ, is upregulated in the airways of asthmatic subjects taking medium daily doses of inhaled budesonide. The biological effects of such genes need to be considered when assessing ICS action.
Funded by AstraZeneca.
- © 2011 ERS