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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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Representative images of immunostaining of sputum cells from asthmatic patients.Case 1 (68-year-old male) and case 2 (72-year-old female) were steroid-naïve patients. Case 3 (79-year-old male) and case 4 (55-year-old female) were patients with severe persistent asthma on high-dose inhaled corticosteroid. Column A: staining with anti-FKBP51 antibody, column B: merged image of staining with anti-major basic protein antibody (MBP) and anti-FKBP51 antibody. Red indicates MBP, and green indicates FKBP51.
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pone-0065284-g005: Representative images of immunostaining of sputum cells from asthmatic patients.Case 1 (68-year-old male) and case 2 (72-year-old female) were steroid-naïve patients. Case 3 (79-year-old male) and case 4 (55-year-old female) were patients with severe persistent asthma on high-dose inhaled corticosteroid. Column A: staining with anti-FKBP51 antibody, column B: merged image of staining with anti-major basic protein antibody (MBP) and anti-FKBP51 antibody. Red indicates MBP, and green indicates FKBP51.

Mentions: Using immunocytochemistry, we observed that FKBP51 expression was qualitatively weaker in sputum eosinophils than in sputum neutrophils and mononuclear cells in steroid-naïve asthmatic patients (Fig. 5, cases 1,2).


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)

Representative images of immunostaining of sputum cells from asthmatic patients.Case 1 (68-year-old male) and case 2 (72-year-old female) were steroid-naïve patients. Case 3 (79-year-old male) and case 4 (55-year-old female) were patients with severe persistent asthma on high-dose inhaled corticosteroid. Column A: staining with anti-FKBP51 antibody, column B: merged image of staining with anti-major basic protein antibody (MBP) and anti-FKBP51 antibody. Red indicates MBP, and green indicates FKBP51.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0065284-g005: Representative images of immunostaining of sputum cells from asthmatic patients.Case 1 (68-year-old male) and case 2 (72-year-old female) were steroid-naïve patients. Case 3 (79-year-old male) and case 4 (55-year-old female) were patients with severe persistent asthma on high-dose inhaled corticosteroid. Column A: staining with anti-FKBP51 antibody, column B: merged image of staining with anti-major basic protein antibody (MBP) and anti-FKBP51 antibody. Red indicates MBP, and green indicates FKBP51.
Mentions: Using immunocytochemistry, we observed that FKBP51 expression was qualitatively weaker in sputum eosinophils than in sputum neutrophils and mononuclear cells in steroid-naïve asthmatic patients (Fig. 5, cases 1,2).

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