title: Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression.
abstract: BACKGROUND
  Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a "leaky" epithelial barrier phenotype. We hypothesize that T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 modulate epithelial junction proteins, thereby contributing to the leaky epithelial barrier.
  
  
  METHODS
  Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis.
  
  
  RESULTS
  IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n = 6) and 68.6% (n = 8) of baseline, respectively. Tight junction protein junctional adhesion molecule-A (JAM-A) expression decreased 42.2% with IL-4 exposure (n = 9) and 37.5% with IL-13 exposure (n = 9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n = 9) and 32.9% with IL-13 exposure (n = 9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or zonula occludens-1 (ZO-1) with IL-4 or IL-13 exposure.
  
  
  CONCLUSIONS
  Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity.
authors: Department of Otolaryngology-Head and Neck Surgery, Emory University, Atlanta, GA.
authors: Sarah K
authors: SK
authors: Wise
authors: Adrienne M
authors: AM
authors: Laury
authors: Elizabeth H
authors: EH
authors: Katz
authors: Kyle A
authors: KA
authors: Den Beste
authors: Charles A
authors: CA
authors: Parkos
authors: Asma
authors: A
authors: Nusrat
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D062446:Claudin-2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D004847:Epithelial Cells / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D018613:Microscopy, Confocal; D009298:Nasal Polyps / Q000276:immunology*; D010256:Paranasal Sinuses / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D062446:Claudin-2; C407243:F11R protein, human; D018793:Interleukin-13; D011956:Receptors, Cell Surface; D015847:Interleukin-4
keywords: IL-13; IL-4; Th2 inflammation; allergic fungal sinusitis; cytokine; epithelial cell; inflammation; interleukin 13; interleukin 4; rhinosinusitis