title: Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression.
abstract: BACKGROUND
  Tight junction (TJ) defects have recently been associated with asthma and chronic rhinosinusitis. The expression, function, and regulation of nasal epithelial TJs remain unknown in patients with allergic rhinitis (AR).
  
  
  OBJECTIVE
  We investigated the expression, function, and regulation of TJs in the nasal epithelium of patients with house dust mite (HDM)-induced AR and in an HDM-induced murine model of allergic airway disease.
  
  
  METHODS
  Air-liquid interface cultures of primary nasal epithelial cells of control subjects and patients with HDM-induced AR were used for measuring transepithelial resistance and passage to fluorescein isothiocyanate-dextran 4 kDa (FD4). Ex vivo transtissue resistance and FD4 permeability of nasal mucosal explants were measured. TJ expression was evaluated by using real-time quantitative PCR and immunofluorescence. In addition, the effects of IL-4, IFN-γ, and fluticasone propionate (FP) on nasal epithelial cells were investigated in vitro. An HDM murine model was used to study the effects of allergic inflammation and FP treatment on transmucosal passage of FD4 in vivo.
  
  
  RESULTS
  A decreased resistance in vitro and ex vivo was found in patients with HDM-induced AR, with increased FD4 permeability and reduced occludin and zonula occludens-1 expression. AR symptoms correlated inversely with resistance in patients with HDM-induced AR. In vitro IL-4 decreased transepithelial resistance and increased FD4 permeability, whereas IFN-γ had no effect. FP prevented IL-4-induced barrier dysfunction in vitro. In an HDM murine model FP prevented the allergen-induced increased mucosal permeability.
  
  
  CONCLUSIONS
  We found impaired nasal epithelial barrier function in patients with HDM-induced AR, with lower occludin and zonula occludens-1 expression. IL-4 disrupted epithelial integrity in vitro, and FP restored barrier function. Better understanding of nasal barrier regulation might lead to a better understanding and treatment of AR.
authors: Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors: Brecht
authors: B
authors: Steelant
authors: Translational Research in Gastro Intestinal Disorders, KU Leuven, Leuven, Belgium.
authors: Ricard
authors: R
authors: Farré
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
authors: Paulina
authors: P
authors: Wawrzyniak
authors: Pediatric Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors: Jochen
authors: J
authors: Belmans
authors: Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Clinical Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.
authors: Emily
authors: E
authors: Dekimpe
authors: Translational Research in Gastro Intestinal Disorders, KU Leuven, Leuven, Belgium.
authors: Hanne
authors: H
authors: Vanheel
authors: Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Clinical Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.
authors: Laura
authors: L
authors: Van Gerven
authors: Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors: Inge
authors: I
authors: Kortekaas Krohn
authors: Pediatric Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors: Dominique M A
authors: DMA
authors: Bullens
authors: Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors: Jan L
authors: JL
authors: Ceuppens
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
authors: Cezmi A
authors: CA
authors: Akdis
authors: Translational Research in Gastro Intestinal Disorders, KU Leuven, Leuven, Belgium.
authors: Guy
authors: G
authors: Boeckxstaens
authors: Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors: Sven F
authors: SF
authors: Seys
authors: Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Clinical Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Otorhinolaryngology, University Hospitals Ghent, Ghent, Belgium; Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: Peter.hellings@med.kuleuven.be.
authors: Peter W
authors: PW
authors: Hellings
mesh_terms: D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003911:Dextrans / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D000068298:Fluticasone / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism*; D062793:Occludin / Q000378:metabolism*; D010539:Permeability; D039981:Pyroglyphidae / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D003911:Dextrans; C568985:OCLN protein, human; D062793:Occludin; D062826:Zonula Occludens-1 Protein; C015219:fluorescein isothiocyanate dextran; D000068298:Fluticasone; D016650:Fluorescein-5-isothiocyanate
keywords: Allergic rhinitis; IL-4; epithelial permeability; epithelial resistance; fluticasone propionate; leak pathway; tight junctions