Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-γ and IL-4
Open accessAbstract
Background Chronic rhinosinusitis (CRS) is a common disease with still unclear pathophysiologic mechanisms. Epithelial tight junctions (TJs) have been shown to be involved in different chronic disorders, including bronchial asthma, inflammatory bowel diseases, and skin disorders. The regulation of epithelial barrier function and TJ expression has not been extensively studied in patients with CRS and in the paranasal sinus epithelium thus far.Objective We sought to elucidate the TJ expression pattern in the epithelium of the sinonasal mucosa and its regulation in patients with CRS.Methods Trans-tissue resistance was measured in biopsy specimens from healthy control subjects and patients with CRS with and without nasal polyps. TJ protein expression was determined by using immunofluorescence, Western blotting, and real-time PCR. Primary epithelial cell cultures from patients with CRS and control subjects were used in air-liquid interface (ALI) cultures for the measurement of transepithelial resistance (TER) and TJ expression. The effect of IFN-γ, IL-4, and IL-17 on ALI cultures was assessed.Results A decreased trans-tissue resistance was found in biopsy specimens from patients with CRS with nasal polyps along with an irregular, patchy, and decreased expression of the TJ molecules occludin and zonula occludens 1. TER was reduced in ALI cultures from patients with CRS with nasal polyps. The cytokines IFN-γ and IL-4 decreased TER, whereas IL-17 did not have any influence on epithelial integrity.Conclusion A defective epithelial barrier was found in patients with CRS with nasal polyps along with a decreased expression of TJ proteins. The disruption of epithelial integrity by IFN-γ and IL-4 in vitro indicates a possible role for these proinflammatory cytokines in the pathogenesis of patients with CRS.
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Epithelial barrier leakiness, particularly of tight junctions sealing the upper and lower respiratory mucosal epithelial surface, has been shown in asthma, AR, and CRS.
“Epithelial barrier leakiness, particularly tight junctions that seal the upper and lower respiratory mucosal epithelial surface, has been shown in asthma, AR and CRS.343,344”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [343]
The Discussion reports defective tight junctions in asthma, and the Results show a disrupted epithelial barrier in CRS, particularly CRS with nasal polyps. The paper mentions reduced barrier function in acute rhinovirus-associated rhinitis, but does not establish it in allergic rhinitis (AR); that part of the claim is unsupported. Page numbers were not provided in our copy. (LLM, conf=0.88)
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- Authors
- Soyka, M. B., Wawrzyniak, P., Eiwegger, T., Holzmann, D., Treis, A., Wanke, K., Kast, J. I., & Akdis, C. A.
- Affiliations
- University of Zurich (CH)
- University Hospital Zurich (CH)
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 130
- Issue
- 5
- Pages
- 1087-1096.e10
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2095499340
- Cited by
- 486
- References
- 45
- Citations by year
- 2026: 29 · 2025: 43 · 2024: 37 · 2023: 41 · 2022: 39 · 2021: 40 · 2020: 42 · 2019: 36 · 2018: 46 · 2017: 32 · 2016: 30 · 2015: 32 · 2014: 24 · 2013: 10 · 2012: 5
- FWCI
- 22.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (132899, 112306)
- Universitätsspital Zürich
- Christine Kühne – Center for Allergy Research and Education
- European Academy of Allergy and Clinical Immunology
- Allergopharma
- Topics
- Health Sciences › Medicine › Otorhinolaryngology › Sinusitis and nasal conditions
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Surgery › Nasal Surgery and Airway Studies
- Keywords
- chronic rhinosinusitis, tight junctions, epithelial barrier function, nasal polyps, interferon-gamma, IL-4, IL-17, occludin, zonula occludens-1, transepithelial electrical resistance, inflammatory cytokines
- MeSH terms
- Biopsy, Cells, Cultured, Chronic Disease, Gene Expression Regulation, Humans, Interferon-gamma, Nasal Mucosa, Nasal Polyps, Rhinitis, Sinusitis, Interleukin-4, Tight Junctions, Interleukin-17, Primary Cell Culture, Claudin-4, Occludin, Zonula Occludens-1 Protein
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