title: Association of eosinophilic inflammation with FKBP51 expression in sputum cells in asthma.
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.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tajiri
authors.forename: Hisako
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Isao
authors.initials: I
authors.lastname: Ito
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oguma
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakaji
authors.forename: Hideki
authors.initials: H
authors.lastname: Inoue
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Iwata
authors.forename: Tadao
authors.initials: T
authors.lastname: Nagasaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kanemitsu
authors.forename: Guergana
authors.initials: G
authors.lastname: Petrova
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003430:Cross-Sectional Studies; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume; D015870:Gene Expression; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000276:immunology; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000305:Adrenal Cortex Hormones; D009569:Nitric Oxide; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5