Expression of glucocorticoid receptors α and β in steroid sensitive and steroid insensitive interstitial lung diseases

Background: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors alpha (GRalpha) and beta (GRbeta). A study was undertaken to assess GRalpha and GRbeta expression in steroid insensitive interstitial lung disease ( idiopathic pulmonary fibrosis (IPF)) and steroid sensitive interstitial lung diseases ( sarcoidosis and cryptogenic organising pneumonia ( COP)). Methods: Lung tissue was obtained from control subjects and from patients with IPF, sarcoidosis, and COP. Pulmonary function tests were carried out at the time of lung biopsy and every 3 months. GRalpha and GRbeta expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25 - 75th percentile. Results: GRalpha mRNA expression (10(5) cDNA copies/mug total RNA) was higher in patients with steroid sensitive interstitial lung diseases ( 10.0; 7.8 - 14.9; n = 11) than in patients with IPF (4.4; 3.2 - 6.6; n = 19; p< 0.001). GR beta expression was at least 1000 times lower than that of GR alpha and did not differ between the three groups. A negative correlation was found between GRa mRNA levels and the fibrotic pathology score of the tissue ( r = -0.484, p< 0.01) and a positive correlation was found between GRalpha mRNA levels and improvement in forced vital capacity ( r = 0.633; p< 0.01) after treatment of patients with glucocorticoids. Immunoreactivity for GR protein was also higher in patients with sarcoidosis and COP than in those with IPF. Conclusion: The variable response of some interstitial lung diseases to steroid treatment may be the result of differences in the expression of GR alpha.