The role of glucocorticoid receptor α and β isoforms in exacerbations of asthma, COPD, and ACOS

Background: Glucocorticoid receptor (GR) β is a well-known antagonist of GR α and it may cause a steroid resistance (SR) in patients with chronic inflammatory or oncological diseases. However, the role of GR α and β in non-SR patients is not determined. Aim: to evaluate GR α, β expression and its clinical role in exacerbations of asthma, COPD, and ACOS. Materials and Methods: The levels of GR α, β mRNAs were measured by real-time PCR in 89 subjects aged 63.4±10.7, namely 22 exacerbated BA, 21 exacerbated COPD, 26 exacerbated ACOS, and 20 controls. DNA samples from all patients were genotyped for the SNP C3435T in the Multidrug Resistance Gene 1 (MDR1). Differences were considered statistically significant when p Results: In asthma patients the GRα/GRβ ratio (α/β) was correlated positively with SpO 2 , and negatively - with duration of hospitalization, bronchodilator reversibility (Δ) of FEF 75 , C 3435 MDR1. In COPD patients, α/β was correlated positively with FEV 1 /FVC, FEV 1 , FEF 50 , FEF 75 , Sgaw, and negatively - with CAT test scjre, frequency of exacerbations and need for O 2 -therapy. In ACOS patients, α/β was correlated positively with FEV 1 and negatively - with ΔFEV 1 , frequency of exacerbations and emergency calls. In all patients systemic glucocorticoids changed GR expression with the highest increasing of GRβ in ACOS. Expression of both GR isoforms was correlated negatively with the severity of pulmonary failure. Conclusion: Increased α/β in asthma, COPD and ACOS patients may be usefull as a prognostic biomarker of favorable course.