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

Tajiri T, Matsumoto H, Niimi A, Ito I, Oguma T, Nakaji H, Inoue H, Iwata T, Nagasaki T, Kanemitsu Y, Petrova G, Mishima M - PLoS ONE (2013)

Bottom Line: Associations between FKBP51 levels and clinical indices were analyzed.No such associations were observed in patients on ICS.Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

ABSTRACT

Background: 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.

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-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.

Results: 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).

Conclusions: Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients.

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Associations between changes in FEV1 after ICS initiation and pretreatment eosinophilic inflammation and FKBP51 levels.Associations between changes in FEV1 after ICS initiation and pretreatment a) blood and b) sputum eosinophil proportions and c) FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in steroid-naïve patients with asthma (n = 20). Abbreviation: FEV1, forced expiratory volume in one second; ICS, inhaled corticosteroid.
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pone-0065284-g004: Associations between changes in FEV1 after ICS initiation and pretreatment eosinophilic inflammation and FKBP51 levels.Associations between changes in FEV1 after ICS initiation and pretreatment a) blood and b) sputum eosinophil proportions and c) FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in steroid-naïve patients with asthma (n = 20). Abbreviation: FEV1, forced expiratory volume in one second; ICS, inhaled corticosteroid.

Mentions: A total of 20 steroid-naïve asthmatic patients were followed up at our hospital. They underwent a 2nd pulmonary function test 11.4±3.8 months later when they were on minimum ICS doses to maintain control (399±241 µg daily equivalent to fluticasone propionate). Changes in FEV1 (24.7±73.7%) from baseline to the 2nd measurement were significantly positively correlated with baseline eosinophil proportions in blood (r = 0.74, p<0.0001) (Fig. 4a) and sputum (r = 0.76, p<0.0001) (Fig. 4b), and were negatively correlated with FKBP51 expression (r = −0.73, p<0.0001) (Fig. 4c). We did not observe any differences in sex, age, baseline FEV1 (% predicted), eosinophil proportions in blood and sputum, or FKBP51 mRNA levels between the 20 patients and the 11 patients who were lost to follow-up.


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

Tajiri T, Matsumoto H, Niimi A, Ito I, Oguma T, Nakaji H, Inoue H, Iwata T, Nagasaki T, Kanemitsu Y, Petrova G, Mishima M - PLoS ONE (2013)

Associations between changes in FEV1 after ICS initiation and pretreatment eosinophilic inflammation and FKBP51 levels.Associations between changes in FEV1 after ICS initiation and pretreatment a) blood and b) sputum eosinophil proportions and c) FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in steroid-naïve patients with asthma (n = 20). Abbreviation: FEV1, forced expiratory volume in one second; ICS, inhaled corticosteroid.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675168&req=5

pone-0065284-g004: Associations between changes in FEV1 after ICS initiation and pretreatment eosinophilic inflammation and FKBP51 levels.Associations between changes in FEV1 after ICS initiation and pretreatment a) blood and b) sputum eosinophil proportions and c) FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in steroid-naïve patients with asthma (n = 20). Abbreviation: FEV1, forced expiratory volume in one second; ICS, inhaled corticosteroid.
Mentions: A total of 20 steroid-naïve asthmatic patients were followed up at our hospital. They underwent a 2nd pulmonary function test 11.4±3.8 months later when they were on minimum ICS doses to maintain control (399±241 µg daily equivalent to fluticasone propionate). Changes in FEV1 (24.7±73.7%) from baseline to the 2nd measurement were significantly positively correlated with baseline eosinophil proportions in blood (r = 0.74, p<0.0001) (Fig. 4a) and sputum (r = 0.76, p<0.0001) (Fig. 4b), and were negatively correlated with FKBP51 expression (r = −0.73, p<0.0001) (Fig. 4c). We did not observe any differences in sex, age, baseline FEV1 (% predicted), eosinophil proportions in blood and sputum, or FKBP51 mRNA levels between the 20 patients and the 11 patients who were lost to follow-up.

Bottom Line: Associations between FKBP51 levels and clinical indices were analyzed.No such associations were observed in patients on ICS.Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

ABSTRACT

Background: 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.

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-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.

Results: 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).

Conclusions: Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naïve asthmatic patients.

Show MeSH
Related in: MedlinePlus