Kathryn L Pothoven1, James E Norton1, Kathryn E Hulse1, Lydia A Suh1, Roderick G Carter1, Erin Rocci2, Kathleen E Harris1, Stephanie Shintani-Smith3, David B Conley3, Rakesh K Chandra3, Mark C Liu4, Atsushi Kato1, Nirmala Gonsalves5, Leslie C Grammer1, Anju T Peters1, Robert C Kern3, Paul J Bryce1, Bruce K Tan3, Robert P Schleimer6. 1. Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. 2. Stritch School of Medicine, Loyola University Chicago, Chicago, Ill. 3. Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. 4. Divisions of Allergy and Clinical Immunology, Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Md. 5. Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. 6. Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address: rpschleimer@northwestern.edu.
Abstract
BACKGROUND: Epithelial barrier dysfunction is thought to play a role in many mucosal diseases, including asthma, chronic rhinosinusitis (CRS), and eosinophilic esophagitis. OBJECTIVE: The objective of this study was to investigate the role of oncostatin M (OSM) in epithelial barrier dysfunction in human mucosal disease. METHODS: OSM expression was measured in tissue extracts, nasal secretions, and bronchoalveolar lavage fluid. The effects of OSM stimulation on barrier function of normal human bronchial epithelial cells and nasal epithelial cells cultured at the air-liquid interface were assessed by using transepithelial electrical resistance and fluorescein isothiocyanate-dextran flux. Dual-color immunofluorescence was used to evaluate the integrity of tight junction structures in cultured epithelial cells. RESULTS: Analysis of samples from patients with CRS showed that OSM mRNA and protein levels were highly increased in nasal polyps compared with those seen in control uncinate tissue (P < .05). OSM levels were also increased in bronchoalveolar lavage fluid of allergic asthmatic patients after segmental allergen challenge and in esophageal biopsy specimens from patients with eosinophilic esophagitis. OSM stimulation of air-liquid interface cultures resulted in reduced barrier function, as measured by decreased transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran flux (P < .05). Alterations in barrier function by OSM were reversible, and the viability of epithelial cells was unaffected. OSM levels in lysates of nasal polyps and uncinate tissue positively correlated with levels of α2-macroglobulin, a marker of epithelial leak, in localized nasal secretions (r = 0.4855, P < .05). CONCLUSIONS: These results suggest that OSM might play a role in epithelial barrier dysfunction in patients with CRS and other mucosal diseases.
BACKGROUND: Epithelial barrier dysfunction is thought to play a role in many mucosal diseases, including asthma, chronic rhinosinusitis (CRS), and eosinophilic esophagitis. OBJECTIVE: The objective of this study was to investigate the role of oncostatin M (OSM) in epithelial barrier dysfunction in humanmucosal disease. METHODS: OSM expression was measured in tissue extracts, nasal secretions, and bronchoalveolar lavage fluid. The effects of OSM stimulation on barrier function of normal human bronchial epithelial cells and nasal epithelial cells cultured at the air-liquid interface were assessed by using transepithelial electrical resistance and fluorescein isothiocyanate-dextran flux. Dual-color immunofluorescence was used to evaluate the integrity of tight junction structures in cultured epithelial cells. RESULTS: Analysis of samples from patients with CRS showed that OSM mRNA and protein levels were highly increased in nasal polyps compared with those seen in control uncinate tissue (P < .05). OSM levels were also increased in bronchoalveolar lavage fluid of allergic asthmaticpatients after segmental allergen challenge and in esophageal biopsy specimens from patients with eosinophilic esophagitis. OSM stimulation of air-liquid interface cultures resulted in reduced barrier function, as measured by decreased transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran flux (P < .05). Alterations in barrier function by OSM were reversible, and the viability of epithelial cells was unaffected. OSM levels in lysates of nasal polyps and uncinate tissue positively correlated with levels of α2-macroglobulin, a marker of epithelial leak, in localized nasal secretions (r = 0.4855, P < .05). CONCLUSIONS: These results suggest that OSM might play a role in epithelial barrier dysfunction in patients with CRS and other mucosal diseases.
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