{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:22:07Z","timestamp":1791073327621,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tight junctions (TJs) play a key role in maintaining bronchial epithelial integrity, including apical-basolateral polarity and paracellular trafficking. Patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) often suffer from chronic infections by the opportunistic Gram-negative bacterium Pseudomonas aeruginosa, which produces multiple virulence factors, including rhamnolipids. The macrolide antibiotic azithromycin (azm) has been shown to improve lung function in patients with CF without reducing the bacterial count within the lung. However, the mechanism of this effect is still debated. It has previously been shown that azm increased transepithelial electrical resistance (TER) in a bronchial epithelial cell line. In this study we used an air\u2013liquid interface model of human airway epithelia and measured TER, changes in TJ expression and architecture after exposure to live P. aeruginosa PAO1, and PAO1-\u0394rhl which is a PAO1 mutant lacking rhlA and rhlB, which encode key enzymes for rhamnolipid production. In addition, the cells were challenged with bacterial culture medium conditioned by these strains, purified rhamnolipids, or synthetic 3O-C12-HSL. Virulence factors secreted by P. aeruginosa reduced TER and caused TJ rearrangement in the bronchial epithelium, exposing the epithelium to further bacterial infiltration. Pretreatment of the bronchial epithelium with azm attenuated this effect and facilitated epithelial recovery. These data suggest that azm protects the bronchial epithelium during P. aeruginosa infection independent of antimicrobial activity, and could explain in part the beneficial results seen in clinical trials of patients with CF.<\/jats:p>","DOI":"10.1165\/rcmb.2008-0357oc","type":"journal-article","created":{"date-parts":[[2009,4,16]],"date-time":"2009-04-16T21:11:34Z","timestamp":1239916294000},"page":"62-68","source":"Crossref","is-referenced-by-count":89,"title":["Azithromycin Maintains Airway Epithelial Integrity during\n                    <i>Pseudomonas aeruginosa<\/i>\n                    Infection"],"prefix":"10.1093","volume":"42","author":[{"given":"Skarphedinn","family":"Halldorsson","sequence":"first","affiliation":[{"name":"Institute of Biology"},{"name":"Biomedical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorarinn","family":"Gudjonsson","sequence":"additional","affiliation":[{"name":"Biomedical Center"},{"name":"Stem Cell Research Unit, Department of Anatomy"},{"name":"Department of Laboratory Hematology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Gottfredsson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and"},{"name":"Faculty of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington, Seattle, Washington; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudmundur Hrafn","family":"Gudmundsson","sequence":"additional","affiliation":[{"name":"Institute of Biology"},{"name":"Biomedical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olafur","family":"Baldursson","sequence":"additional","affiliation":[{"name":"Biomedical Center"},{"name":"Faculty of Pharmacy, University of Iceland, Reykjavik, Iceland"},{"name":"Department of Pulmonary Medicine, Landspitali University Hospital, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,1,1]]},"reference":[{"key":"2026030623262633100_bib1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1172\/JCI0215209","volume":"109","year":"2002","journal-title":"J Clin Invest"},{"key":"2026030623262633100_bib2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1183\/09031936.03.00098803","volume":"23","year":"2004","journal-title":"Eur Respir J"},{"key":"2026030623262633100_bib3","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1513\/pats.2306013","volume":"1","year":"2004","journal-title":"Proc Am Thorac Soc"},{"key":"2026030623262633100_bib4","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.arcmed.2007.02.003","volume":"38","year":"2007","journal-title":"Arch Med Res"},{"key":"2026030623262633100_bib5","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/01.mnh.0000232883.43093.76","volume":"15","year":"2006","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2026030623262633100_bib6","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1016\/j.febslet.2007.05.051","volume":"581","year":"2007","journal-title":"FEBS Lett"},{"key":"2026030623262633100_bib7","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1146\/annurev.cellbio.22.010305.104219","volume":"22","year":"2006","journal-title":"Annu Rev Cell Dev Biol"},{"key":"2026030623262633100_bib8","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1146\/annurev.physiol.68.040104.131404","volume":"68","year":"2006","journal-title":"Annu Rev Physiol"},{"key":"2026030623262633100_bib9","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1165\/ajrcmb.20.5.3408","volume":"20","year":"1999","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026030623262633100_bib10","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1128\/iai.65.7.2861-2867.1997","volume":"65","year":"1997","journal-title":"Infect Immun"},{"key":"2026030623262633100_bib11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1369-5274(03)00008-0","volume":"6","year":"2003","journal-title":"Curr Opin Microbiol"},{"key":"2026030623262633100_bib12","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1128\/JB.01567-07","volume":"190","year":"2008","journal-title":"J Bacteriol"},{"key":"2026030623262633100_bib13","doi-asserted-by":"crossref","first-page":"6921","DOI":"10.1016\/j.febslet.2006.11.057","volume":"580","year":"2006","journal-title":"FEBS Lett"},{"key":"2026030623262633100_bib14","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.1128\/IAI.01772-05","volume":"74","year":"2006","journal-title":"Infect Immun"},{"key":"2026030623262633100_bib15","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.coph.2006.12.005","volume":"7","year":"2007","journal-title":"Curr Opin Pharmacol"},{"key":"2026030623262633100_bib16","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1089\/hum.2006.192","volume":"18","year":"2007","journal-title":"Hum Gene Ther"},{"key":"2026030623262633100_bib17","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1128\/AAC.50.5.1805-1812.2006","volume":"50","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"2026030623262633100_bib18","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1001\/jama.290.13.1749","volume":"290","year":"2003","journal-title":"JAMA"},{"key":"2026030623262633100_bib19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jac\/dkh309","volume":"54","year":"2004","journal-title":"J Antimicrob Chemother"},{"key":"2026030623262633100_bib20","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.bbrc.2006.09.132","volume":"350","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"2026030623262633100_bib21","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1128\/JCM.42.12.5842-5845.2004","volume":"42","year":"2004","journal-title":"J Clin Microbiol"},{"key":"2026030623262633100_bib22","first-page":"283","volume":"43","year":"2007","journal-title":"In Vitro Cell Dev Biol"},{"key":"2026030623262633100_bib23","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1242\/jcs.00830","volume":"116","year":"2003","journal-title":"J Cell Sci"},{"key":"2026030623262633100_bib24","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1165\/ajrcmb\/7.5.485","volume":"7","year":"1992","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026030623262633100_bib25","first-page":"151","volume":"11","year":"2004","journal-title":"Can Respir J"},{"key":"2026030623262633100_bib26","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/nature01440","volume":"422","year":"2003","journal-title":"Nature"},{"key":"2026030623262633100_bib27","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1007\/s00253-005-0150-3","volume":"68","year":"2005","journal-title":"Appl Microbiol Biotechnol"},{"key":"2026030623262633100_bib28","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1152\/jappl.1992.72.6.2271","volume":"72","year":"1992","journal-title":"J Appl Physiol"},{"key":"2026030623262633100_bib29","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1046\/j.1462-2920.2000.00136.x","volume":"2","year":"2000","journal-title":"Environ Microbiol"},{"key":"2026030623262633100_bib30","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1128\/IAI.70.4.1783-1790.2002","volume":"70","year":"2002","journal-title":"Infect Immun"},{"key":"2026030623262633100_bib31","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.drudis.2007.11.005","volume":"13","year":"2008","journal-title":"Drug Discov Today"},{"key":"2026030623262633100_bib32","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1083\/jcb.136.2.399","volume":"136","year":"1997","journal-title":"J Cell Biol"},{"key":"2026030623262633100_bib33","doi-asserted-by":"crossref","first-page":"6395","DOI":"10.4049\/jimmunol.178.10.6395","volume":"178","year":"2007","journal-title":"J Immunol"},{"key":"2026030623262633100_bib34","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1164\/rccm.200709-1413OC","volume":"177","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2026030623262633100_bib35","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1183\/09031936.06.00131805","volume":"28","year":"2006","journal-title":"Eur Respir J"},{"key":"2026030623262633100_bib36","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ijantimicag.2007.08.001","volume":"31","year":"2008","journal-title":"Int J Antimicrob Agents"},{"key":"2026030623262633100_bib37","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.coph.2008.01.010","volume":"8","year":"2008","journal-title":"Curr Opin Pharmacol"},{"key":"2026030623262633100_bib38","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1128\/AAC.01142-06","volume":"51","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"2026030623262633100_bib39","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1128\/AAC.01011-06","volume":"51","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"key":"2026030623262633100_bib40","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1128\/AAC.45.6.1930-1933.2001","volume":"45","year":"2001","journal-title":"Antimicrob Agents Chemother"},{"key":"2026030623262633100_bib41","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1136\/thx.2005.057950","volume":"61","year":"2006","journal-title":"Thorax"},{"key":"2026030623262633100_bib42","first-page":"1026","volume":"1","year":"1987","journal-title":"Lancet"},{"key":"2026030623262633100_bib43","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1093\/jac\/dkn059","volume":"61","year":"2008","journal-title":"J Antimicrob Chemother"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/42\/1\/62\/67078274\/ajrcmb_42_1_62.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/42\/1\/62\/67078274\/ajrcmb_42_1_62.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T04:28:14Z","timestamp":1772857694000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/42\/1\/62\/8493861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,1]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2010,1,1]]},"published-print":{"date-parts":[[2010,1,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2008-0357oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,1]]},"published":{"date-parts":[[2010,1,1]]}}}