{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:46:41Z","timestamp":1793386001617,"version":"4.5.0"},"reference-count":40,"publisher":"European Respiratory Society (ERS)","issue":"6","funder":[{"DOI":"10.13039\/100005640","name":"Flight Attendant Medical Research Institute","doi-asserted-by":"publisher","award":["FAMRI CIA 123046"],"award-info":[{"award-number":["FAMRI CIA 123046"]}],"id":[{"id":"10.13039\/100005640","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BWH-LRRI Consortium"},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["P01 HL114501"],"award-info":[{"award-number":["P01 HL114501"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["P50 HL107165-01"],"award-info":[{"award-number":["P50 HL107165-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R01 AI111475"],"award-info":[{"award-number":["R01 AI111475"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","award":["R21 HL111835"],"award-info":[{"award-number":["R21 HL111835"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2014,12,6]]},"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Club cell secretory protein-16 (CC16) is the major secreted product of airway club cells, but its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unclear. We measured CC16 airway expression in humans with and without COPD and CC16 function in a cigarette smoke (CS)-induced COPD murine model.<\/jats:p>\n                  <jats:p>\n                    Airway CC16 expression was measured in COPD patients, smokers without COPD and non-smokers. We exposed wildtype (WT) and\n                    <jats:italic>\n                      CC16\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice to CS or air for up to 6\u2005months, and measured airway CC16 expression, pulmonary inflammation, alveolar septal cell apoptosis, airspace enlargement, airway mucin 5AC (MUC5AC) expression, small airway remodelling and pulmonary function.\n                  <\/jats:p>\n                  <jats:p>\n                    Smokers and COPD patients had reduced airway CC16 immunostaining that decreased with increasing COPD severity. Exposing mice to CS reduced airway CC16 expression.\n                    <jats:italic>\n                      CC16\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice had greater CS-induced emphysema, airway remodelling, pulmonary inflammation, alveolar cell apoptosis, airway MUC5AC expression, and more compliant lungs than WT mice. These changes were associated with increased nuclear factor-\u03baB (NF-\u03baB) activation in\n                    <jats:italic>\n                      CC16\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    lungs. CS-induced acute pulmonary changes were reversed by adenoviral-mediated over-expression of CC16.\n                  <\/jats:p>\n                  <jats:p>CC16 protects lungs from CS-induced injury by reducing lung NF-\u03baB activation. CS-induced airway CC16 deficiency increases CS-induced pulmonary inflammation and injury and likely contributes to the pathogenesis of COPD.<\/jats:p>","DOI":"10.1183\/09031936.00134214","type":"journal-article","created":{"date-parts":[[2015,2,21]],"date-time":"2015-02-21T00:31:08Z","timestamp":1424478668000},"page":"1544-1556","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":137,"title":["Protective role for club cell secretory protein-16 (CC16) in the development of COPD"],"prefix":"10.1183","volume":"45","author":[{"given":"Maria E.","family":"Laucho-Contreras","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Polverino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kushagra","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emer","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Pinto-Plata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Divo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Ashfaq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Stripp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aprile L.","family":"Pilon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohannes","family":"Tesfaigzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartolome R.","family":"Celli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2015,2,19]]},"reference":[{"key":"2024102023190434000_45.6.1544.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1201534"},{"key":"2024102023190434000_45.6.1544.2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2147\/COPD.S2089","article-title":"Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease","volume":"3","author":"Owen","year":"2008","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"2024102023190434000_45.6.1544.3","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2008.098483"},{"key":"2024102023190434000_45.6.1544.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105482"},{"key":"2024102023190434000_45.6.1544.5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201105-0831OC"},{"key":"2024102023190434000_45.6.1544.6","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201106-0992OC"},{"key":"2024102023190434000_45.6.1544.7","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2008.102574"},{"key":"2024102023190434000_45.6.1544.8","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201305-0892OC"},{"key":"2024102023190434000_45.6.1544.9","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.27.2.200200270c"},{"key":"2024102023190434000_45.6.1544.10","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1994.1145"},{"key":"2024102023190434000_45.6.1544.11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3025"},{"key":"2024102023190434000_45.6.1544.12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.1051"},{"key":"2024102023190434000_45.6.1544.13","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1006\/enrs.1994.1047","article-title":"Serum Clara cell protein: an indicator of bronchial cell dysfunction caused by tobacco smoking","volume":"66","author":"Bernard","year":"1994","journal-title":"Environ Res"},{"key":"2024102023190434000_45.6.1544.14","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.1.9904073"},{"key":"2024102023190434000_45.6.1544.15","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000158354.39635.AB"},{"key":"2024102023190434000_45.6.1544.16","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0923"},{"key":"2024102023190434000_45.6.1544.17","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4066"},{"key":"2024102023190434000_45.6.1544.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(01)02636-4"},{"key":"2024102023190434000_45.6.1544.19","first-page":"L656","article-title":"Clara cell secretory protein: a determinant of PCB bioaccumulation in mammals","volume":"271","author":"Stripp","year":"1996","journal-title":"Am J Physiol"},{"key":"2024102023190434000_45.6.1544.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035960"},{"key":"2024102023190434000_45.6.1544.21","doi-asserted-by":"crossref","first-page":"19081","DOI":"10.1016\/S0021-9258(17)32277-9","article-title":"Heterologous expression of human uteroglobin\/polychlorinated biphenyl-binding protein. Determination of ligand binding parameters and mechanism of phospholipase A2 inhibition in vitro","volume":"269","author":"Andersson","year":"1994","journal-title":"J Biol Chem"},{"key":"2024102023190434000_45.6.1544.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.03.045"},{"key":"2024102023190434000_45.6.1544.23","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.1.9912137"},{"key":"2024102023190434000_45.6.1544.24","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0295OC"},{"key":"2024102023190434000_45.6.1544.25","doi-asserted-by":"publisher","DOI":"10.3109\/01902148709064309"},{"key":"2024102023190434000_45.6.1544.26","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.21.1.3630"},{"key":"2024102023190434000_45.6.1544.27","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201206-1013OC"},{"key":"2024102023190434000_45.6.1544.28","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt326"},{"key":"2024102023190434000_45.6.1544.29","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-008-9103-1"},{"key":"2024102023190434000_45.6.1544.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2005.10.027"},{"key":"2024102023190434000_45.6.1544.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010679200"},{"key":"2024102023190434000_45.6.1544.32","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0353OC"},{"key":"2024102023190434000_45.6.1544.33","doi-asserted-by":"crossref","first-page":"793505","DOI":"10.1155\/2013\/793505","article-title":"The involvement of phospholipases A2 in asthma and chronic obstructive pulmonary disease","volume":"2013","author":"Pniewska","year":"2013","journal-title":"Mediators Inflamm"},{"key":"2024102023190434000_45.6.1544.34","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0038OC"},{"key":"2024102023190434000_45.6.1544.35","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201103-0468OC"},{"key":"2024102023190434000_45.6.1544.36","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.068353"},{"key":"2024102023190434000_45.6.1544.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(99)70192-7"},{"key":"2024102023190434000_45.6.1544.38","doi-asserted-by":"publisher","DOI":"10.1038\/12458"},{"key":"2024102023190434000_45.6.1544.39","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5317.1408"},{"key":"2024102023190434000_45.6.1544.40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.10.2939"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/09031936.00134214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T01:55:19Z","timestamp":1740362119000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/09031936.00134214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,19]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,5,31]]},"published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1183\/09031936.00134214"],"URL":"https:\/\/doi.org\/10.1183\/09031936.00134214","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,19]]}}}