Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 130, Issue 5, Pages 1087-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.05.052
Keywords
Chronic rhinosinusitis; chronic sinusitis; tight junctions; occludin; claudin; zonula occludens; regulation; cytokines; leaky epithelium
Categories
Funding
- European Allergy and Asthma Center Davos (EACD)
- Swiss National Science Foundation [32-132899, 32-112306]
- Christine Kuhne Center for Allergy Research and Education (CK-CARE)
- Muller-Gierok-Foundation
- University Hospital Zurich
- Muller-Gierok Foundation
- European Allergy and Asthma Center Davos
- Swiss National Foundation
- CK-CARE
- Novartis
- PREDICTA
- Swiss National Science Foundation
- MeDALL
- Global Allergy and Asthma European Network
Ask authors/readers for more resources
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-gamma, 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-gamma 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-gamma and IL-4 in vitro indicates a possible role for these proinflammatory cytokines in the pathogenesis of patients with CRS. (J Allergy Clin Immunol 2012;130:1087-96.)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available