@article{7155d3682a984b86a46ae08eee864fff,
title = "Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease",
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.",
keywords = "Oncostatin M, atopic asthma, chronic rhinosinusitis, eosinophilic esophagitis, epithelial barrier, tight junctions, transepithelial electrical resistance",
author = "Pothoven, {Kathryn L.} and Norton, {James E.} and Hulse, {Kathryn E.} and Suh, {Lydia A.} and Carter, {Roderick G.} and Erin Rocci and Harris, {Kathleen E.} and Stephanie Shintani-Smith and Conley, {David B.} and Chandra, {Rakesh K.} and Liu, {Mark C.} and Atsushi Kato and Nirmala Gonsalves and Grammer, {Leslie C.} and Peters, {Anju T.} and Kern, {Robert C.} and Bryce, {Paul J.} and Tan, {Bruce K.} and Schleimer, {Robert P.}",
note = "Funding Information: Supported in part by grants R37HL068546 , R01HL078860 , U19AI106683 , and T32AI007476-16 from the National Institutes of Health and by the Ernest S. Bazley Foundation . Funding Information: Disclosure of potential conflict of interest: This study was funded by the National Institutes of Health (NIH) and the Ernest S. Bazley Foundation . K. L. Pothoven's institution has received funding from the NIH . S. Shintani-Smith's institution has received funding from the Triological Society (American College of Surgeons Career Scientist Award). R. K. Chandra's institution has received funding from the NIH . A. Kato's institution has received funding from the NIH . L. C. Grammer's institution has received funding from the Bazley Foundation and the NIH , from which she also received support for travel; she is employed by Northwestern University and the Northwestern Medical Faulty Foundation, which has received or has grants pending from the Bazley Foundation, the NIH, the Food Allergy Network, and S&C Electric; she has received consultancy fees from Astellas Pharmaceuticals; she has received payment for delivering lectures from the American Academy of Allergy, Asthma & Immunology and Mount Sinai; and she receives royalties from Lippincott, UpToDate, BMJ, and Elsevier. A. T. Peters has received consultancy fees from Greer Laboratories and payment for delivering lectures from Baxter. P. J. Bryce's institution has received funding from the National Institute of Allergy and Infectious Diseases ( R01AI076456 and R01AI05839 ). B. K. Tan's institution has received funding from the NIH ( K23 DC012067 ). R. P. Schleimer has received funding from the NIH . The rest of the authors declare that they have no other relevant conflicts of interest. Funding Information: We thank Rebecca A. Krier-Burris, Jingfei Li, Christopher J. Ocampo, and Joshua B. Wechsler for their technical assistance, manuscript review, lively discussion, and helpful suggestions. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Publisher Copyright: {\textcopyright} 2015 American Academy of Allergy, Asthma & Immunology.",
year = "2015",
month = sep,
day = "1",
doi = "10.1016/j.jaci.2015.01.043",
language = "English (US)",
volume = "136",
pages = "737--746.e4",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",
}