title: Protocadherin-1 is a glucocorticoid-responsive critical regulator of airway epithelial barrier function.
abstract: BACKGROUND
  Impaired epithelial barrier function renders the airway vulnerable to environmental triggers associated with the pathogenesis of bronchial asthma. We investigated the influence of protocadherin-1 (PCDH1), a susceptibility gene for bronchial hyperresponsiveness, on airway epithelial barrier function.
  
  
  METHODS
  We applied transepithelial electric resistance and dextran permeability testing to evaluate the barrier function of cultured airway epithelial cells. We studied PCDH1 function by siRNA-mediated knockdown and analyzed nasal or bronchial tissues from 16 patients with chronic rhinosinusitis (CRS) and nine patients with bronchial asthma for PCDH1 expression.
  
  
  RESULTS
  PCDH1 was upregulated with the development of epithelial barrier function in cultured airway epithelial cells. Immunocytochemical analysis revealed that PCDH localized to cell-cell contact sites and colocalized with E-cadherin at the apical site of airway epithelial cells. PCDH1 gene knockdown disrupted both tight and adhesion junctions. Immunohistochemical analysis revealed strong PCDH1 expression in nasal and bronchial epithelial cells; however, expression decreased in inflamed tissues sampled from patients with CRS or bronchial asthma. Dexamethasone (Dex) increased the barrier function of airway epithelial cells and increased PCDH1 expression. PCDH1 gene knockdown eradicated the effect of Dex on barrier function.
  
  
  CONCLUSIONS
  These results suggest that PCDH1 is important for airway function as a physical barrier, and its dysfunction is involved in the pathogenesis of allergic airway inflammation. We also suggest that glucocorticoids promotes epithelial barrier integrity by inducing PCDH1.
authors.affiliation: Nihon University School of Medicine Division of Respiratory Disease, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. blackflag@onyx.ocn.ne.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kozu
authors.affiliation: Nihon University School of Medicine Division of Respiratory Disease, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. gon.yasuhiro@nihon-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Gon
authors.affiliation: Nihon University School of Medicine Division of Respiratory Disease, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. maruoka.shuichiro@nihon-u.ac.jp.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Maruoka
authors.affiliation: Nihon University School of Medicine Division of Microbiology, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. kuroda.kazumichi@nihon-u.ac.jp.
authors.forename: Kuroda
authors.initials: K
authors.lastname: Kazumichi
authors.affiliation: Nihon University School of Medicine Division of Respiratory Disease, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. akiko.wish@key.ocn.ne.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sekiyama
authors.affiliation: Nihon University School of Medicine Division of Otolaryngology, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. kishi.hiroyuki@nihon-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.affiliation: Nihon University School of Medicine Division of Otolaryngology, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. nomusan@siren.ocn.ne.jp.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Nihon University School of Medicine Division of Otolaryngology, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. ikeda.minoru@nihon-u.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Nihon University School of Medicine Division of Respiratory Disease, 30-1 Ohyaguchi-Kamicho, Itabashiku, Tokyo, 173-8610, Japan. shuh@med.nihon-u.ac.jp.
authors.forename: Shu
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001249:Asthma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000091363:Protocadherins; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000378:metabolism; D055815:Young Adult
chemical_list: D015820:Cadherins; D005938:Glucocorticoids; C081683:PCDH1 protein, human; D000091363:Protocadherins; D012313:RNA