Association of Eosinophilic Inflammation with FKBP51 Expression in Sputum Cells in Asthma.

Abstract

[Background]: Airway eosinophilia is a predictor of steroid responsiveness in steroid-naı¨ve asthma. However, the relationship between airway eosinophilia and the expression of FK506-binding protein 51 (FKBP51), a glucocorticoid receptor cochaperone that plays a role in steroid insensitivity in asthma, remains unknown. [Objective]: To evaluate the relationship between eosinophilic inflammation and FKBP51 expression in sputum cells in asthma. [Methods]: The FKBP51 mRNA levels in sputum cells from steroid-naı¨ve patients with asthma (n = 31) and stable asthmatic patients on inhaled corticosteroid (ICS) (n = 28) were cross-sectionally examined using real-time PCR. Associations between FKBP51 levels and clinical indices were analyzed. [Results]: In steroid-naı¨ve patients, the FKBP51 levels were negatively correlated with eosinophil proportions in blood (r =20.52) and sputum (r =20.57), and exhaled nitric oxide levels (r =20.42) (all p,0.05). No such associations were observed in patients on ICS. In steroid-naı¨ve patients, improvement in forced expiratory volume in one second after ICS initiation was correlated with baseline eosinophil proportions in blood (r = 0.74) and sputum (r = 0.76) and negatively correlated with FKBP51 levels (r =20.73) (all p,0.0001) (n = 20). Lastly, the FKBP51 levels were the lowest in steroid-naı¨ve asthmatic patients, followed by mild to moderate persistent asthmatic patients on ICS, and the highest in severe persistent asthmatic patients on ICS (p,0.0001). [Conclusions]: Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naı¨ve asthmatic patients.