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

Tomoko Tajiri,Hideki Inoue,Akio Niimi,Isao Ito,Guergana Petrova,Yoshihiro Kanemitsu,Tsuyoshi Oguma,Hisako Matsumoto,Hitoshi Nakaji,Tadao Nagasaki,Toshiyuki Iwata,Michiaki Mishima,Heinz Fehrenbach

doi:10.1371/journal.pone.0065284

Abstract

BackgroundAirway eosinophilia is a predictor of steroid responsiveness in steroid-naïve asthma. However, the relationship between airway eosinophilia and the expression of FK506-binding protein 51 (FKBP51), a glucocorticoid receptor co-chaperone that plays a role in steroid insensitivity in asthma, remains unknown.ObjectiveTo evaluate the relationship between eosinophilic inflammation and FKBP51 expression in sputum cells in asthma.MethodsThe FKBP51 mRNA levels in sputum cells from steroid-naïve 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.ResultsIn steroid-naïve patients, the FKBP51 levels were negatively correlated with eosinophil proportions in blood (r = −0.52) and sputum (r = −0.57), and exhaled nitric oxide levels (r = −0.42) (all p<0.05). No such associations were observed in patients on ICS. In steroid-naïve 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 = −0.73) (all p<0.0001) (n = 20). Lastly, the FKBP51 levels were the lowest in steroid-naïve 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).ConclusionsLower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients.

Highlights

Asthma is a chronic inflammatory disorder of the airways in which eosinophils, Th2 cells, and Th2-type cytokines play a role [1]
We examined FK506-binding protein 51 (FKBP51) expression in induced sputum cells in patients with asthma to test the hypothesis that the level of FKBP51 expression is down-regulated in eosinophilic inflammation in steroid-naıve asthma, and that this downregulation disappears in patients on inhaled corticosteroid (ICS) treatment
The RNA quality indicator (RQI) was independent of the cell type; no association was found between RQI and proportion of cell type (neutrophils (r = 20.06, p = 0.67), mononuclear cells (r = 0.15, p = 0.29), or eosinophils (r = 0.09, p = 0.54))

Summary

Introduction

Asthma is a chronic inflammatory disorder of the airways in which eosinophils, Th2 cells, and Th2-type cytokines play a role [1]. Eosinophilia in asthma is responsive to GC; steroidnaıve asthmatic patients with blood [3,4] or sputum [3,5] eosinophilia show greater improvement in lung function after GC treatment than patients without eosinophilia. In steroid-naıve patients with asthma, lower expression of FKBP51 mRNA in airway epithelial cells [9] and in peripheral blood mononuclear cells [10] is correlated with greater improvement in lung function after GC treatment, suggesting that low expression of FKBP51 may be a mechanism underlying the GC sensitivity. 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

Methods

Results

Conclusion