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

PLoS One. 2013 Jun 6;8(6):e65284. doi: 10.1371/journal.pone.0065284. Print 2013.

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.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Asthma / drug therapy
  • Asthma / genetics*
  • Asthma / immunology
  • Asthma / pathology
  • Cross-Sectional Studies
  • Eosinophils / immunology*
  • Eosinophils / pathology
  • Exhalation
  • Female
  • Forced Expiratory Volume
  • Gene Expression
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Real-Time Polymerase Chain Reaction
  • Severity of Illness Index
  • Sputum / cytology
  • Tacrolimus Binding Proteins / genetics*
  • Tacrolimus Binding Proteins / immunology

Substances

  • Adrenal Cortex Hormones
  • Nitric Oxide
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5

Grants and funding

The authors have no support or funding to report.