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

Abstract

Background: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors α (GRα) and β (GRβ). A study was undertaken to assess GRα and GRβ 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. GRα and GRβ expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 25–75th percentile. Results: GRα mRNA expression (10⁵ cDNA copies/µg 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). GRβ expression was at least 1000 times lower than that of GRα and did not differ between the three groups. A negative correlation was found between GRα mRNA levels and the fibrotic pathology score of the tissue (r = −0.484, p<0.01) and a positive correlation was found between GRα 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 GRα.