Association of eosinophilic inflammation with FKBP51 expression in sputum cells in asthma.

Association of eosinophilic inflammation with FKBP51 expression in sputum cells in asthma.
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DOI:
10.1371/journal.pone.0065284
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Mishima M
Mishima M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tajiri T;Matsumoto H;Niimi A;Ito I;Oguma T;Nakaji H;Inoue H;Iwata T;Nagasaki T;Kanemitsu Y;Petrova G;Mishima M

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气道嗜酸性粒细胞增多是steroid-naïve哮喘患者类固醇反应性的预测因子。然而,气道嗜酸性粒细胞增加与fk506结合蛋白51 (FKBP51)表达之间的关系尚不清楚,fk506结合蛋白51是一种糖皮质激素受体共伴侣,在哮喘的类固醇不敏感中起作用。探讨哮喘患者痰细胞中FKBP51表达与嗜酸性粒细胞炎症的关系。采用real-time PCR横断面检测steroid-naïve哮喘患者(n = 31)和吸入皮质类固醇(ICS)的稳定哮喘患者(n = 28)痰细胞中FKBP51 mRNA水平。分析FKBP51水平与临床指标的相关性。在steroid-naïve患者中,FKBP51水平与血液中嗜酸性粒细胞比例(r = - 0.52)、痰中(r = - 0.57)、呼出一氧化氮水平(r = - 0.42)呈负相关(均p<0.05)。在ICS患者中没有观察到这种关联。在steroid-naïve患者中,ICS启动后1秒内用力呼气量的改善与血液(r = 0.74)和痰(r = 0.76)的基线嗜酸性粒细胞比例相关,与FKBP51水平负相关(r = - 0.73)(均p<0.0001) (n = 20)。最后,FKBP51水平在steroid-naïve哮喘患者中最低,其次是ICS组的轻中度持续性哮喘患者,ICS组的重度持续性哮喘患者中最高(p<0.0001)。痰细胞中FKBP51的低表达可能反映steroid-naïve哮喘患者的嗜酸性炎症和糖皮质激素反应性。
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.
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作者:
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通讯作者: European Respiratory Society
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发表时间: 2008-03-01
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