{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T03:08:28Z","timestamp":1786504108076,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T00:00:00Z","timestamp":1522108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["NMRC\/CIRG\/1458\/2016"],"award-info":[{"award-number":["NMRC\/CIRG\/1458\/2016"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170897"],"award-info":[{"award-number":["81170897"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81441028"],"award-info":[{"award-number":["81441028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 receptor \u03b12 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b12) is a receptor for <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 which has conflicting roles in mediating <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 responses in the lower airway, with little known about its impact on upper airway diseases. We sought to investigate the expression of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 receptors, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b11 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b12, in chronically inflamed nasal epithelium, and explore <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010induced signaling pathways in an in\u00a0vitro model of human nasal epithelial cells (<jats:styled-content style=\"fixed-case\">hNEC<\/jats:styled-content>s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The protein and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression levels of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 and its receptors in nasal biopsies of patients with nasal polyps (<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 (10\u00a0ng\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>, 72\u00a0hours) treatment in <jats:styled-content style=\"fixed-case\">hNEC<\/jats:styled-content>s using a pseudostratified epithelium in air\u2010liquid interface (<jats:styled-content style=\"fixed-case\">ALI<\/jats:styled-content>) culture.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were significant increases in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b11, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b12 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels in <jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> epithelium with healthy controls as baseline. <jats:styled-content style=\"fixed-case\">MUC<\/jats:styled-content>5<jats:styled-content style=\"fixed-case\">AC mRNA<\/jats:styled-content> positively correlated with <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b12 (<jats:italic>r<\/jats:italic>\u00a0=\u00a0.5886, <jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>.002) but not with <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b11 in primary <jats:styled-content style=\"fixed-case\">hNEC<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 treatment resulted in a significant increase in <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b12 only in <jats:styled-content style=\"fixed-case\">hNEC<\/jats:styled-content>s. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013 treatment induced an activation of extracellular signal\u2010regulated kinases (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>)1\/2 and an upregulation of C\u2010<jats:styled-content style=\"fixed-case\">JUN<\/jats:styled-content>, where the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010induced effects on <jats:styled-content style=\"fixed-case\">hNEC<\/jats:styled-content>s could be attenuated by <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 inhibitor (50\u00a0\u03bcmol\/L) or dexamethasone (10<jats:sup>\u22124<\/jats:sup>\u201010<jats:sup>\u22127<\/jats:sup>\u00a0mol\/L) treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b12 has a potential role in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013\u2010induced <jats:styled-content style=\"fixed-case\">MUC<\/jats:styled-content>5<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content> and ciliary changes through <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 signal pathway in the nasal epithelium. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013R\u03b12 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.13424","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T11:36:39Z","timestamp":1517916999000},"page":"1673-1685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Role of <scp>IL<\/scp>\u201013R\u03b12 in modulating <scp>IL<\/scp>\u201013\u2010induced <scp>MUC<\/scp>5<scp>AC<\/scp> and ciliary changes in healthy and <scp>CRS<\/scp>w<scp>NP<\/scp> mucosa"],"prefix":"10.1111","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7511-0680","authenticated-orcid":false,"given":"J.","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. Y.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. K.","family":"Andiappan","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network (SIgN) Agency for Science, Technology and Research (A*STAR) Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. S.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. H.","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. T.","family":"Thong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery National University Health System (NUHS) Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. K.","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery National University Health System (NUHS) Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. G.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. B.","family":"Low","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. L.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology The Second Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0909-2963","authenticated-orcid":false,"given":"D. Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Yong Loo Lin School of Medicine National University of Singapore Singapore 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