{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:35:11Z","timestamp":1791668111266,"version":"4.3.4"},"reference-count":65,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["GALIET19G0"],"award-info":[{"award-number":["GALIET19G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"crossref","award":["TMLGCBX16TT"],"award-info":[{"award-number":["TMLGCBX16TT"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"crossref","award":["GSA21C004"],"award-info":[{"award-number":["GSA21C004"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"crossref","award":["Vertex Innovation Award"],"award-info":[{"award-number":["Vertex Innovation Award"]}],"id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondazione Italiana per la Ricerca sulla Fibrosi Cistica","award":["FFC#9\/2022"],"award-info":[{"award-number":["FFC#9\/2022"]}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"crossref","award":["TMLGMFU22TT"],"award-info":[{"award-number":["TMLGMFU22TT"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,22]]},"abstract":"<jats:p>The fluid covering the surface of airway epithelia represents a first barrier against pathogens. The chemical and physical properties of the airway surface fluid are controlled by the activity of ion channels and transporters. In cystic fibrosis (CF), loss of CFTR chloride channel function causes airway surface dehydration, bacterial infection, and inflammation. We investigated the effects of IL-17A plus TNF-\u03b1, 2 cytokines with relevant roles in CF and other chronic lung diseases. Transcriptome analysis revealed a profound change with upregulation of several genes involved in ion transport, antibacterial defense, and neutrophil recruitment. At the functional level, bronchial epithelia treated in vitro with the cytokine combination showed upregulation of ENaC channel, ATP12A proton pump, ADRB2 \u03b2-adrenergic receptor, and SLC26A4 anion exchanger. The overall result of IL-17A\/TNF-\u03b1 treatment was hyperviscosity of the airway surface, as demonstrated by fluorescence recovery after photobleaching (FRAP) experiments. Importantly, stimulation with a \u03b2-adrenergic agonist switched airway surface to a low-viscosity state in non-CF but not in CF epithelia. Our study suggests that CF lung disease is sustained by a vicious cycle in which epithelia cannot exit from the hyperviscous state, thus perpetuating the proinflammatory airway surface condition.<\/jats:p>","DOI":"10.1172\/jci.insight.164944","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T12:00:26Z","timestamp":1665489626000},"source":"Crossref","is-referenced-by-count":24,"title":["Airway surface hyperviscosity and defective mucociliary transport by IL-17\/TNF-\u03b1 are corrected by \u03b2-adrenergic stimulus"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9301-8095","authenticated-orcid":true,"given":"Daniela","family":"Guidone","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6307-3755","authenticated-orcid":true,"given":"Martina","family":"Buccirossi","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-4800","authenticated-orcid":true,"given":"Paolo","family":"Scudieri","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, Genova, Italy."},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genova, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Genovese","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6001-9892","authenticated-orcid":true,"given":"Sergio","family":"Sarnataro","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8526-8692","authenticated-orcid":true,"given":"Rossella","family":"De Cegli","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-5374","authenticated-orcid":true,"given":"Federico","family":"Cresta","sequence":"additional","affiliation":[{"name":"Centro Fibrosi Cistica, IRCCS Istituto Giannina Gaslini, Genova, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-4424","authenticated-orcid":true,"given":"Vito","family":"Terlizzi","sequence":"additional","affiliation":[{"name":"Meyer Children\u2019s Hospital, Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Firenze, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7314-8837","authenticated-orcid":true,"given":"Gabrielle","family":"Planelles","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM UMRS 1138, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France."},{"name":"CNRS EMR 8228, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-9124","authenticated-orcid":true,"given":"Gilles","family":"Crambert","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM UMRS 1138, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9, Paris, France."},{"name":"CNRS EMR 8228, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Sermet","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades\/INSERM U1151, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8686-3461","authenticated-orcid":true,"given":"Luis J.V.","family":"Galietta","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy."},{"name":"Department of Translational Medical Sciences (DISMET), University of Napoli \u201cFederico II\u201d, Napoli, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215217"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028241"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1042\/BST20170402"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00285.2017"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00098803"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.018"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.10.007"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/781087"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22330"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0244OC"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.240838"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/srep36016"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255825"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38662"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120562"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nature11130"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00576-6"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102755"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81724-9"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/science.1223012"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.266734"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2018-0158OC"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.09.007"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123616"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5589"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092090"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0468-5"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI125669"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00112.2020"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163518"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00311.2001"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.2.839"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00440.2002"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI150398"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0827-z"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.010908.163108"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.148155"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.20028559"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708555200"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7052"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009111168"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73935"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600223R"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.7150\/thno.46417"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0349OC"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511184103"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c200012"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017322"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kve045"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00036.2012"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1106695108"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2729"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103263"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20444-8"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00716-2019"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150918"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311999110"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.05.012"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/164944\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:27:35Z","timestamp":1779146855000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/164944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,22]]},"references-count":65,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11,22]]},"published-print":{"date-parts":[[2022,11,22]]}},"alternative-id":["10.1172\/jci.insight.164944"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.164944","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,22]]},"article-number":"e164944"}}