{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:37Z","timestamp":1787013997628,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T00:00:00Z","timestamp":1537228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["(HI4C2628)ROK"],"award-info":[{"award-number":["(HI4C2628)ROK"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Clinical features of aspirin\u2010exacerbated respiratory disease (\n AERD<\/jats:styled-content>\n ) are characterized by overproduction of cysteinyl leukotrienes (\n LT<\/jats:styled-content>\n ) and eosinophil activation, in which epithelial cells contribute to eosinophilic airway inflammation. Folliculin (\n FLCN<\/jats:styled-content>\n ) helps maintain the integrity of epithelial barrier, but little is known about\n FLCN<\/jats:styled-content>\n in\n AERD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n We investigated the role of\n FLCN<\/jats:styled-content>\n in the pathogenic mechanisms of\n AERD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We recruited 178 subjects with\n AERD<\/jats:styled-content>\n , 276 subjects with aspirin\u2010tolerant asthma (\n ATA<\/jats:styled-content>\n ) and 71 normal healthy controls (\n NC<\/jats:styled-content>\n ) at Ajou Medical Center. Levels of\n FLCN<\/jats:styled-content>\n and interleukin (\n IL<\/jats:styled-content>\n )\u20108 in sera and supernatants were measured by\n ELISA<\/jats:styled-content>\n . Peripheral blood eosinophils isolated from asthmatic patients were cocultured with human airway epithelial cells (\n HAEC<\/jats:styled-content>\n s) pretreated with\n LTE<\/jats:styled-content>\n 4<\/jats:sub>\n , dexamethasone and montelukast. The intracellular expressions of\n FLCN<\/jats:styled-content>\n , tight (\n TJ<\/jats:styled-content>\n ) (occludins, claudin\u20101) and adherens (\n AJ<\/jats:styled-content>\n ) junctions (E\u2010cadherin) were analysed by Western blotting. sh\n RNA<\/jats:styled-content>\n was used to down\u2010regulate\n \n FLCN<\/jats:styled-content>\n <\/jats:italic>\n (\n \n sh\n FLCN<\/jats:styled-content>\n <\/jats:italic>\n ) in\n HAEC<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Serum\n FLCN<\/jats:styled-content>\n levels were significantly higher in\n AERD<\/jats:styled-content>\n group than in\n ATA<\/jats:styled-content>\n and\n NC<\/jats:styled-content>\n groups (all\n P<\/jats:italic>\n < 0.001). The cut\u2010off value of 56.6 pg\/\n mL<\/jats:styled-content>\n was used to define the high\n FLCN<\/jats:styled-content>\n phenotype (high\n FLCN<\/jats:styled-content>\n ). Asthmatic patients with high\n FLCN<\/jats:styled-content>\n were associated with increased airway hyperresponsiveness to methacholine (\n P<\/jats:italic>\n = 0.015). The serum\n FLCN<\/jats:styled-content>\n level could discriminate\n AERD<\/jats:styled-content>\n group from\n NC<\/jats:styled-content>\n group with 82% sensitivity (\n AUC<\/jats:styled-content>\n = 0.793,\n P<\/jats:italic>\n < 0.001). When\n HAEC<\/jats:styled-content>\n s were exposed to\n LTE<\/jats:styled-content>\n 4<\/jats:sub>\n ,\n FLCN<\/jats:styled-content>\n release was increased significantly (\n P<\/jats:italic>\n < 0.05), which were amplified along with disruption of\n TJ<\/jats:styled-content>\n and\n AJ<\/jats:styled-content>\n expressions when\n HAEC<\/jats:styled-content>\n s were cocultured with eosinophils and\n LTE<\/jats:styled-content>\n 4<\/jats:sub>\n (all\n P<\/jats:italic>\n < 0.05); these effects were suppressed by dexamethasone and montelukast.\n \n FLCN<\/jats:styled-content>\n <\/jats:italic>\n knockdown reduced\n IL<\/jats:styled-content>\n \u20108 release and occludin expression from\n \n sh\n FLCN<\/jats:styled-content>\n <\/jats:italic>\n HAEC<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings suggest that high\n LT<\/jats:styled-content>\n and airway eosinophilia increased\n FLCN<\/jats:styled-content>\n release from\n HAEC<\/jats:styled-content>\n s, which enhance epithelial activation and disruption. Modulation of\n FLCN<\/jats:styled-content>\n may be a potential target for\n AERD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cea.13253","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T11:09:34Z","timestamp":1534936174000},"page":"1464-1473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Epithelial folliculin enhances airway inflammation in aspirin\u2010exacerbated respiratory disease"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-788X","authenticated-orcid":false,"given":"Hoang Kim Tu","family":"Trinh","sequence":"first","affiliation":[{"name":"Department of Allergy & Clinical Immunology Ajou University School of Medicine Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5382-9283","authenticated-orcid":false,"given":"Duy Le","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Medicine and Pharmacy at Ho Chi Minh city Ho Chi Minh city Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8384-9557","authenticated-orcid":false,"given":"Youngwoo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Allergy & Clinical Immunology Ajou University School of Medicine Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-261X","authenticated-orcid":false,"given":"Hyun\u2010Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"Translational Research Laboratory for Inflammatory Disease Clinical Trial Center Ajou University Medical Center Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-8964","authenticated-orcid":false,"given":"Seung\u2010Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Allergy & Clinical Immunology Ajou University School of Medicine Suwon South Korea"},{"name":"Translational Research Laboratory for Inflammatory Disease Clinical Trial Center Ajou University Medical Center Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2614-0303","authenticated-orcid":false,"given":"Hae\u2010Sim","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Allergy & Clinical Immunology Ajou University School of Medicine Suwon South Korea"},{"name":"Translational Research Laboratory for Inflammatory Disease Clinical Trial Center Ajou University Medical Center Suwon South Korea"},{"name":"Department of Biomedical Sciences The Graduate School Ajou University School of Medicine Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2015.7.4.312"},{"issue":"676","key":"e_1_2_7_3_1","first-page":"e1","article-title":"Prevalence of aspirin\u2010exacerbated respiratory disease among asthmatic patients: a meta\u2010analysis of the literature","volume":"135","author":"Rajan JP","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.09.025"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2016.06.005"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2016.8.4.298"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2016.06.008"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.05.049"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200504-031AC"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.01.022"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4018"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2002.01362.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603781103"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.07603.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djm288"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00104-6"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.03.025"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12107"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.180"},{"key":"e_1_2_7_20_1","unstructured":"Global Initiative for Asthma.2017GINA Report Global Strategy for Asthma Management and Prevention.http:\/\/ginasthma.org\/. 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