{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:08:54Z","timestamp":1781309334076,"version":"3.54.1"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","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":[[2019,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Asthma is a chronic inflammatory condition of the airways and patients sensitized to airborne fungi such as <jats:italic>Aspergillus fumigatus<\/jats:italic> have more severe asthma. Thickening of the bronchial subepithelial layer is a contributing factor to asthma severity for which no current treatment exists. Airway epithelium acts as an initial defence barrier to inhaled spores, orchestrating an inflammatory response and contributing to subepithelial fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to analyse the production of pro\u2010fibrogenic factors by airway epithelium in response to <jats:italic>A\u00a0fumigatus<\/jats:italic>, in order to propose novel anti\u2010fibrotic strategies for fungal\u2010induced asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the induction of key pro\u2010fibrogenic factors, TGF\u2010\u03b21, TGF\u2010\u03b22, periostin and endothelin\u20101, by human airway epithelial cells and in mice exposed to <jats:italic>A\u00a0fumigatus<\/jats:italic> spores or secreted fungal factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Aspergillus fumigatus<\/jats:italic> specifically caused production of endothelin\u20101 by epithelial cells in vitro but not any of the other pro\u2010fibrogenic factors assessed. <jats:italic>A\u00a0fumigatus<\/jats:italic> also induced endothelin\u20101 in murine lungs, associated with extensive inflammation and airway remodelling. Using a selective endothelin\u20101 receptor antagonist, we demonstrated for the first time that endothelin\u20101 drives many features of airway remodelling and inflammation elicited by <jats:italic>A\u00a0fumigatus<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings are consistent with the hypothesis that elevated endothelin\u20101 levels contribute to subepithelial thickening and highlight this factor as a possible therapeutic target for difficult\u2010to\u2010treat fungal\u2010induced asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13367","type":"journal-article","created":{"date-parts":[[2019,2,9]],"date-time":"2019-02-09T02:09:43Z","timestamp":1549678183000},"page":"861-873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Endothelin\u20101 mediates <i>Aspergillus fumigatus<\/i>\u2010induced airway inflammation and remodelling"],"prefix":"10.1111","volume":"49","author":[{"given":"Briony","family":"Labram","sequence":"first","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine Faculty of Biology Medicine and Health School of Biological Sciences University of Manchester  Manchester UK"},{"name":"Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5571-368X","authenticated-orcid":false,"given":"Sara","family":"Namvar","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine Faculty of Biology Medicine and Health School of Biological Sciences University of Manchester  Manchester UK"},{"name":"Manchester Academic Health Science Centre  Manchester UK"},{"name":"Environment and Life Sciences University of Salford  Greater Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7186-6141","authenticated-orcid":false,"given":"Tracy","family":"Hussell","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Science Centre  Manchester UK"},{"name":"Manchester Collaborative Centre for Inflammation Research (MCCIR) University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9085-5664","authenticated-orcid":false,"given":"Sarah E.","family":"Herrick","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine Faculty of Biology Medicine and Health School of Biological Sciences University of Manchester  Manchester UK"},{"name":"Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21547"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200702-212OC"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3038.2005.00239.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/318029"},{"key":"e_1_2_7_6_1","first-page":"316049","article-title":"Mechanisms of remodeling in asthmatic airways","volume":"2012","author":"Shifren A","year":"2012","journal-title":"J Allergy (Cairo)"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-7022-4-14"},{"issue":"8","key":"e_1_2_7_8_1","first-page":"936","article-title":"Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta\u2010analysis","volume":"13","author":"Agarwal R","year":"2009","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.56.012302.160625"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206291"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0011RT"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.08.046"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2013.12.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof4010008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1513\/pats.2306034"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135720"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2000.106210"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7763"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12426"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.3.2733"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.09.034"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.02.046"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13181"},{"issue":"4","key":"e_1_2_7_24_1","first-page":"1034","article-title":"Endothelin in bronchoalveolar lavage fluid and its relation to airflow obstruction in asthma","volume":"151","author":"Redington AE","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770909509089497"},{"issue":"4","key":"e_1_2_7_26_1","first-page":"365","article-title":"Circulating endothelin\u20101 levels in patients with bronchial asthma","volume":"73","author":"Aoki T","year":"1994","journal-title":"Ann Allergy"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/rr44"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.61"},{"issue":"3","key":"e_1_2_7_29_1","first-page":"981","article-title":"Transforming growth factors\u2010beta 1, \u2010beta 2, and \u2010beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin\u2010induced lung fibrosis","volume":"150","author":"Coker RK","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311430200"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.05.029"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009674"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03840.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.102"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(97)70148-9"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.09.023"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23134"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0502"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/4.1.50"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2009.02.007"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.2.189"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011833"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/147616"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.155.6.9196091"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00076.2002"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1159\/000080338"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01256.x"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(97)00194-0"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201301-0132OC"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0446OC"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.12271"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1081\/JAS-120023579"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0010030"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.005488-0"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/619614"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0062OC"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.funbio.2012.07.004"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201797"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029906"},{"issue":"6","key":"e_1_2_7_60_1","first-page":"419","article-title":"Epithelial cell apoptosis and lung remodeling","volume":"4","author":"Kuwano K","year":"2007","journal-title":"Cell Mol Immunol"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200909-1350OC"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0121OC"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64775-X"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.11.035"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/146.5_Pt_1.1320"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/652632"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770903.2013.769266"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.13367","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13367","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cea.13367","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T14:07:59Z","timestamp":1694354879000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.13367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,18]]},"references-count":66,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1111\/cea.13367"],"URL":"https:\/\/doi.org\/10.1111\/cea.13367","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,18]]},"assertion":[{"value":"2018-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}