Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
PLoS One. 2013 Jun 6;8(6):e65284. doi: 10.1371/journal.pone.0065284. Print 2013.
Airway 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.
To evaluate the relationship between eosinophilic inflammation and FKBP51 expression in sputum cells in asthma.
The 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.
In 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).
Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients.
气道嗜酸性粒细胞增多是初治哮喘患者对类固醇反应性的预测指标。然而,气道嗜酸性粒细胞增多与 FK506 结合蛋白 51(FKBP51)表达之间的关系,FKBP51 是一种糖皮质激素受体共伴侣,在哮喘中发挥类固醇不敏感作用,目前尚不清楚。
评估哮喘患者痰细胞中嗜酸性粒细胞炎症与 FKBP51 表达之间的关系。
使用实时 PCR 检测初治哮喘患者(n = 31)和吸入皮质类固醇(ICS)稳定哮喘患者(n = 28)痰细胞中的 FKBP51 mRNA 水平。分析 FKBP51 水平与临床指标之间的关系。
在初治哮喘患者中,FKBP51 水平与血液(r = -0.52)和痰(r = -0.57)嗜酸性粒细胞比例以及呼气一氧化氮水平(r = -0.42)呈负相关(均 p<0.05)。在 ICS 治疗的患者中未观察到这种相关性。在初治哮喘患者中,ICS 起始后用力呼气量的改善与基线时血液(r = 0.74)和痰(r = 0.76)嗜酸性粒细胞比例呈正相关,与 FKBP51 水平呈负相关(r = -0.73)(均 p<0.0001)(n = 20)。最后,FKBP51 水平在初治哮喘患者中最低,其次是 ICS 治疗的轻度至中度持续性哮喘患者,ICS 治疗的重度持续性哮喘患者最高(p<0.0001)。
痰细胞中 FKBP51 表达降低可能反映初治哮喘患者的嗜酸性粒细胞炎症和糖皮质激素反应性。