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Author Notes:

Correspondence: Sarah K. Wise, M.D., Department of Otolaryngology-Head and Neck Surgery, Emory University, 550 Peachtree Street, MOT 9th Floor, Atlanta, GA 30308. Phone: (404) 686-7241. Fax: (404) 686-4540. Email: skmille@emory.edu

Disclosures: Approval for this study was granted by the Institutional Review Board of Emory University.

Authors declare no potential conflicts of interest.

Subject:

Research Funding:

This work was supported in part by the following funding sources:

Short Term Training in Health Professional Schools, National Institutes of Health T35-HL007473 (K.A.D.)

American Rhinologic Society New Investigator Award (S.K.W.)

Clinical and Translational Science Award Program, National Institutes of Health, National Center for Research Resources KL2 RR0025009 and UL1 RR025008 (S.K.W.)

Structure function studies in intestinal epithelial JAM, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases DK061379 (C.A.P.)

Neutrophil interactions with intestinal epithelial cells, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, DK072564 (C.A.P.)

Intestinal epithelial tight junction structure-function, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, DK059888 (A.N.)

Keywords:

  • Adherens junction
  • allergic fungal rhinosinusitis
  • allergic rhinitis
  • claudin-2
  • E-cadherin
  • epithelial permeability
  • junction adhesion molecule-A
  • occludin
  • sinonasal epithelium
  • tight junction

Epithelial Permeability Alterations in an In Vitro Air-Liquid Interface Model of Allergic Fungal Rhinosinusitis

Tools:

Journal Title:

International Forum of Allergy and Rhinology

Volume:

Volume 3, Number 1

Publisher:

, Pages 19-25

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background Chronic rhinosinusitis (CRS) is an inflammatory upper-airway disease with numerous etiologies. Patients with a characteristic subtype of CRS, allergic fungal rhinosinusitis (AFRS), display increased expression of Th2 cytokines and antigen-specific IgE. Various sinonasal inflammatory conditions are associated with alterations in epithelial barrier function. The aim of this study was to compare epithelial permeability and intercellular junctional protein expression amongst cultured primary sinonasal cells from AFRS patients versus non-inflammatory controls. Methods Epithelial cells isolated from paranasal sinus mucosa of AFRS and non-inflammatory control patients were grown to confluence on permeable supports and transitioned to air-liquid interface (ALI). Trans-epithelial resistance (TER) was measured with a horizontal Ussing chamber to characterize the functional permeability of each cell type. After TER recordings were complete, a panel of intercellular junctional proteins was assessed by Western blot and immunofluorescence labeling followed by confocal microscopy. Results After 12 samples were measured from each group, we observed a 41% mean decrease in TER in AFRS cells (296±89 ohms × cm2) compared to control (503±134 ohms × cm2, P=0.006). TER deficits observed in AFRS were associated with decreased expression of the tight junction proteins occludin and Junctional Adhesion Molecule-A (JAM-A), and increased expression of a leaky tight junction protein claudin-2. Conclusions Cultured sinonasal epithelium from AFRS patients displayed increased epithelial permeability and altered expression of intercellular junctional proteins. Given that these cells were not incubated with inflammatory cytokines in vitro, the cultured AFRS epithelial alterations may represent a retained modification in protein expression from the in vivo phenotype.

Copyright information:

© 2013 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC

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