PMID- 22927233 OWN - NLM STAT- MEDLINE DCOM- 20130705 LR - 20211021 IS - 2042-6984 (Electronic) IS - 2042-6976 (Print) IS - 2042-6976 (Linking) VI - 3 IP - 1 DP - 2013 Jan TI - Epithelial permeability alterations in an in vitro air-liquid interface model of allergic fungal rhinosinusitis. PG - 19-25 LID - 10.1002/alr.21077 [doi] AB - 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 T helper 2 (Th2) cytokines and antigen-specific immunoglobulin E (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 among cultured primary sinonasal cells from AFRS patients vs noninflammatory controls. METHODS: Epithelial cells isolated from paranasal sinus mucosa of AFRS and noninflammatory control patients were grown to confluence on permeable supports and transitioned to air-liquid interface (ALI). Transepithelial 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 x cm(2) ) compared to control (503 +/- 134 ohms x cm(2) , 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. CONCLUSION: 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. CI - Copyright (c) 2013 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC. FAU - Den Beste, Kyle A AU - Den Beste KA AD - Epithelial Pathobiology and Mucosal Inflammation Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30308, USA. FAU - Hoddeson, Elizabeth K AU - Hoddeson EK FAU - Parkos, Charles A AU - Parkos CA FAU - Nusrat, Asma AU - Nusrat A FAU - Wise, Sarah K AU - Wise SK LA - eng GR - DK072564/DK/NIDDK NIH HHS/United States GR - KL2 TR000455/TR/NCATS NIH HHS/United States GR - T35-HL007473/HL/NHLBI NIH HHS/United States GR - DK061379/DK/NIDDK NIH HHS/United States GR - R01 DK072564/DK/NIDDK NIH HHS/United States GR - KL2 RR025009/RR/NCRR NIH HHS/United States GR - UL1 TR000454/TR/NCATS NIH HHS/United States GR - T35 HL007473/HL/NHLBI NIH HHS/United States GR - UL1 RR025008/RR/NCRR NIH HHS/United States GR - R01 DK059888/DK/NIDDK NIH HHS/United States GR - R01 DK061379/DK/NIDDK NIH HHS/United States GR - DK059888/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120827 PL - United States TA - Int Forum Allergy Rhinol JT - International forum of allergy & rhinology JID - 101550261 RN - 0 (Claudin-2) RN - 0 (Junctional Adhesion Molecule A) RN - 0 (Occludin) SB - IM MH - Blotting, Western MH - Claudin-2/metabolism MH - Epithelial Cells/*metabolism MH - Humans MH - Intercellular Junctions/*metabolism MH - Intracellular Membranes/*metabolism MH - Junctional Adhesion Molecule A/metabolism MH - Microscopy, Confocal MH - Occludin/metabolism MH - Paranasal Sinuses/*metabolism MH - Permeability MH - Rhinitis/*metabolism MH - Sinusitis/*metabolism MH - Tight Junctions/metabolism PMC - PMC3511593 MID - NIHMS391104 COIS- Conflict of Interest Disclosure: [Table: see text] EDAT- 2012/08/29 06:00 MHDA- 2013/07/06 06:00 PMCR- 2014/01/01 CRDT- 2012/08/29 06:00 PHST- 2012/02/28 00:00 [received] PHST- 2012/05/14 00:00 [revised] PHST- 2012/06/12 00:00 [accepted] PHST- 2012/08/29 06:00 [entrez] PHST- 2012/08/29 06:00 [pubmed] PHST- 2013/07/06 06:00 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - 10.1002/alr.21077 [doi] PST - ppublish SO - Int Forum Allergy Rhinol. 2013 Jan;3(1):19-25. doi: 10.1002/alr.21077. Epub 2012 Aug 27.