{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:02:50Z","timestamp":1790413370985,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100003572","name":"American Academy of Otolaryngic Allergy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003572","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010836","name":"American Laryngological, Rhinological and Otological Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>In the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP), <jats:italic>Aspergillus fumigatus (A. fumigatus)<\/jats:italic> can upregulate IL\u201033 from human sinonasal epithelial cells (SNECs), which then activates innate lymphoid cells causing release of IL\u201013, an important driver of allergic inflammation. However, the mechanism by which <jats:italic>A. fumigatus<\/jats:italic> mediates the induction of IL\u201033 expression remains to be elucidated. The objectives of this study were to determine the specific fungal component(s) and the receptor responsible for mediating the <jats:italic>A. fumigatus<\/jats:italic> induced increase in IL\u201033 expression in SNECs from patients with CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SNECs from CRSwNP patients were cultured and stimulated with various fungal components in the absence or presence of 4\u2010(2\u2010Aminoethyl)benzenesulfonyl fluoride hydrochloride, an irreversible serine protease inhibitor, or GB83, a reversible protease activated receptor 2 (PAR2) inhibitor. IL\u201033 expression was evaluated using quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR). PAR2 expression was examined in inflamed mucosa from nonatopic control and CRSwNP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Elevation of IL\u201033 expression in primary SNECs was found in response to fungal protease but not fungal cell wall components. PAR2 expression was elevated in inflamed mucosa from CRSwNP patients in comparison to controls. The <jats:italic>A. fumigatus<\/jats:italic> fungal protease\u2010mediated elevation in IL\u201033 expression by human SNECs was serine protease\u2010 and PAR2\u2010dependent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data suggest that serine protease activity of <jats:italic>A. fumigatus<\/jats:italic> is capable of inducing IL\u201033 expression in CRSwNP SNECs via PAR2, a potential therapeutic target in the treatment of CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA<\/jats:p><jats:p><jats:italic>Laryngoscope<\/jats:italic>, 129:2230\u20132235, 2019<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.28000","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T04:52:39Z","timestamp":1555044759000},"page":"2230-2235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["<i>Aspergillus fumigatus<\/i> induction of IL\u201033 expression in chronic rhinosinusitis is PAR2\u2010dependent"],"prefix":"10.1002","volume":"129","author":[{"given":"Caroline J.","family":"Dietz","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery McGovern Medical School at the University of Texas Health Science Center  Houston Texas U.S.A"},{"name":"the Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine McGovern Medical School at the University of Texas Health Science Center  Houston Texas U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery McGovern Medical School at the University of Texas Health Science Center  Houston Texas U.S.A"},{"name":"the Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine McGovern Medical School at the University of Texas Health Science Center  Houston 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