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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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FKBP51 levels in induced sputum cells in patients with asthma.FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in induced sputum cells became progressively higher from steroid-naïve asthmatic patients (naïve, n = 31), to mild to moderate asthmatic patients on inhaled corticosteroid (mild to moderate, n = 6), and then to severe persistent asthmatic patients on inhaled corticosteroid (severe, n = 22) (p<0.0001 by the Kruskal-Wallis test). *Significant by the Wilcoxon rank-sum test. Values and bars represent means.
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pone-0065284-g001: FKBP51 levels in induced sputum cells in patients with asthma.FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in induced sputum cells became progressively higher from steroid-naïve asthmatic patients (naïve, n = 31), to mild to moderate asthmatic patients on inhaled corticosteroid (mild to moderate, n = 6), and then to severe persistent asthmatic patients on inhaled corticosteroid (severe, n = 22) (p<0.0001 by the Kruskal-Wallis test). *Significant by the Wilcoxon rank-sum test. Values and bars represent means.

Mentions: The level of FKBP51 expression in induced sputum cells in steroid-naïve patients with asthma was significantly lower than that in patients on ICS (p<0.0001) (Fig. 1). In steroid-naïve patients with asthma, FKBP51 expression was significantly inversely correlated with eosinophil proportions in blood (r = −0.52, p = 0.003) and sputum (r = −0.57, p = 0.0008) (Fig. 2a, b), and with FeNO levels (r = −0.42, p = 0.019) (Fig. 2c). The significant correlation between FKBP51 expression and sputum eosinophil proportions remained even after the right most and lowest outlier in Fig. 2b was excluded from the analysis (r = −0.45, p = 0.013). When using a second order regression equation for FKBP51 expression levels and sputum eosinophil proportions in steroid-naïve patients with asthma, FKBP51 expression in a sputum non-eosinophil cell (i.e., neutrophil, mononuclear cell, or lymphocyte) was estimated to be 6.1 times higher than that in a sputum eosinophil. We applied 100 to “sputum eosinophil proportion” in the equation of “log10FKBP51 (expression normalized to β2MG) = 0.948 − 0.246 × (log10 sputum eosinophil proportion) − 0.101 × (log10 sputum eosinophil proportion − 0.246)2″ to estimate FKBP51 expression in a sputum eosinophil, whereas 0.01 was used to estimate FKBP51 expression in a non-eosinophil cell.


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)

FKBP51 levels in induced sputum cells in patients with asthma.FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in induced sputum cells became progressively higher from steroid-naïve asthmatic patients (naïve, n = 31), to mild to moderate asthmatic patients on inhaled corticosteroid (mild to moderate, n = 6), and then to severe persistent asthmatic patients on inhaled corticosteroid (severe, n = 22) (p<0.0001 by the Kruskal-Wallis test). *Significant by the Wilcoxon rank-sum test. Values and bars represent means.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065284-g001: FKBP51 levels in induced sputum cells in patients with asthma.FKBP51 mRNA levels normalized to β2 microglobulin mRNA levels in induced sputum cells became progressively higher from steroid-naïve asthmatic patients (naïve, n = 31), to mild to moderate asthmatic patients on inhaled corticosteroid (mild to moderate, n = 6), and then to severe persistent asthmatic patients on inhaled corticosteroid (severe, n = 22) (p<0.0001 by the Kruskal-Wallis test). *Significant by the Wilcoxon rank-sum test. Values and bars represent means.
Mentions: The level of FKBP51 expression in induced sputum cells in steroid-naïve patients with asthma was significantly lower than that in patients on ICS (p<0.0001) (Fig. 1). In steroid-naïve patients with asthma, FKBP51 expression was significantly inversely correlated with eosinophil proportions in blood (r = −0.52, p = 0.003) and sputum (r = −0.57, p = 0.0008) (Fig. 2a, b), and with FeNO levels (r = −0.42, p = 0.019) (Fig. 2c). The significant correlation between FKBP51 expression and sputum eosinophil proportions remained even after the right most and lowest outlier in Fig. 2b was excluded from the analysis (r = −0.45, p = 0.013). When using a second order regression equation for FKBP51 expression levels and sputum eosinophil proportions in steroid-naïve patients with asthma, FKBP51 expression in a sputum non-eosinophil cell (i.e., neutrophil, mononuclear cell, or lymphocyte) was estimated to be 6.1 times higher than that in a sputum eosinophil. We applied 100 to “sputum eosinophil proportion” in the equation of “log10FKBP51 (expression normalized to β2MG) = 0.948 − 0.246 × (log10 sputum eosinophil proportion) − 0.101 × (log10 sputum eosinophil proportion − 0.246)2″ to estimate FKBP51 expression in a sputum eosinophil, whereas 0.01 was used to estimate FKBP51 expression in a non-eosinophil cell.

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