{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:17:56Z","timestamp":1791231476580,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T00:00:00Z","timestamp":1485993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23ES020859"],"award-info":[{"award-number":["K23ES020859"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Dysregulated sinonasal epithelial cell (SNEC) barrier function has been proposed to contribute to the pathogenesis of sinonasal inflammatory conditions such as allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Allergens such as house dust mite (HDM) have been reported to disrupt SNEC barrier integrity. We have recently identified nuclear erythroid 2\u2010related factor 2 (Nrf2) activation via sulforaphane (SFN) stimulation to stabilize SNEC barrier function. The purpose of this study was to explore whether Nrf2 activation could ameliorate HDM\u2010induced SNEC barrier dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human SNECs (HSNECs) were grown from patients at the air\u2010liquid interface (ALI). HSNECs were stimulated with HDM with or without pharmacologic activation of Nrf2 with SFN. HSNECs were then stained for the epithelial cell junction protein zonula occludens\u20101 (ZO\u20101) and cell surface localization was evaluated by confocal microscopy. Transepithelial electrical resistance (TER) and paracellular fluorescein isothiocyanate (FITC)\u2010dextran permeability was measured in response to stimulation with HDM and SFN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HDM stimulation caused a global disruption of the protein ZO\u20101 along with an associated decrease in TER (<jats:italic>p<\/jats:italic> &lt; 0.001) and increased FITC\u2010dextran paracellular permeability (<jats:italic>p<\/jats:italic> &lt; 0.0001). Enhancing Nrf2 activation through treatment with SFN prior to stimulation with HDM was associated with increased localization of ZO\u20101 at the cell surface and statistically significant increases in TER (<jats:italic>p<\/jats:italic> &lt; 0.05) and decrease in paracellular FITC\u2010dextran permeability (<jats:italic>p<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first study to demonstrate that HDM\u2010induced SNEC barrier dysfunction may be preventable by Nrf2 activation. The Nrf2 antioxidant pathway may represent a potential therapeutic target for allergen\u2010induced sinonasal inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.21916","type":"journal-article","created":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T12:33:45Z","timestamp":1486038825000},"page":"536-541","source":"Crossref","is-referenced-by-count":29,"title":["Nuclear erythroid 2\u2010related factor 2 activation inhibits house dust mite\u2013induced sinonasal epithelial cell barrier dysfunction"],"prefix":"10.1002","volume":"7","author":[{"suffix":"Jr.","given":"Nyall R.","family":"London","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Tharakan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Biswal","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences The Johns Hopkins Bloomberg School of Public Health  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Murugappan","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599814561600"},{"key":"e_1_2_6_3_1","first-page":"69","article-title":"The role of innate immunity and aeroallergens in chronic rhinosinusitis","volume":"79","author":"London NR","year":"2016","journal-title":"Adv Otorhinolaryngol"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.05.052"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2016.30.4295"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/lio2.21"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5844"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21168"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.050"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00398.2014"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.06.027"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21827"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2007.21.3034"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21237"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21646"}],"container-title":["International Forum of Allergy &amp; Rhinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Falr.21916","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.21916","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T02:46:11Z","timestamp":1696646771000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/alr.21916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,2]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/alr.21916"],"URL":"https:\/\/doi.org\/10.1002\/alr.21916","archive":["Portico"],"relation":{},"ISSN":["2042-6976","2042-6984"],"issn-type":[{"value":"2042-6976","type":"print"},{"value":"2042-6984","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,2]]}}}