Glucocorticoid receptor mRNA levels in bronchial epithelial cells of patients with COPD: influence of glucocorticoids

Abstract

Glucocorticoids (gcs) are known to be effective in the treatment of asthma. In chronic obstructive pulmonary disease (COPD), however, no beneficial effects are demonstrated in most patients. Hypothetically, this may be explained by an overexpressed β-glucocorticoid receptor (GR) compared to the α-GR. The aim of this study was to investigate α- and β-GR mRNA levels and ratios in patients with COPD with or without glucocorticoid treatment. GR and, as a control, metallothionein (MT) 2 mRNA levels were compared between patients with COPD receiving glucocorticoids (COPD + gcs), glucocorticoid naive COPD-patients (COPD − gcs) and non-COPD control patients not using gcs. Bronchoscopy was performed and bronchial epithelial cells were sampled with brushing. Smoking did not influence α- and β-GR levels and ratios, nor the MT2 mRNA expression level. The α-GR mRNA expression was lower in the COPD − gcs group than in controls. Both GR forms were higher in the COPD+ gcs patients than in the COPD − gcs patients, but not different from the levels measured in the controls. α1 β - GR mRNA ratios did not differ between the groups and averaged 1·7, suggesting no inhibitory effect of the β-GR on the α1 form. MT2 levels were upregulated in the COPD + gcs patients as compared to the COPD − gcs group, indicating a pharmacological glucocorticoid effect. In the present study it is demonstrated that basal GR mRNA levels are lower in patients with COPD. Although this needs to be investigated further, this might explain, in part, the non-responsiveness of patients with COPD to gcs.