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dc.contributor.authorJoelsson, Jon P
dc.contributor.authorMyszor, Iwona T
dc.contributor.authorSigurdsson, Snaevar
dc.contributor.authorLehmann, Fredrik
dc.contributor.authorPage, Clive P
dc.contributor.authorGudmundsson, Gudmundur H
dc.contributor.authorGudjonsson, Thorarinn
dc.contributor.authorKarason, Sigurbergur
dc.date.accessioned2021-03-01T10:53:31Z
dc.date.available2021-03-01T10:53:31Z
dc.date.issued2020-05-19
dc.date.submitted2021-03
dc.identifier.citationJoelsson, J. P., Myszor, I. T., Sigurdsson, S., Lehmann, F., Page, C. P., Gudmundsson, G. H., . . . Karason, S. (2020). Azithromycin has lung barrier protective effects in a cell model mimicking ventilator-induced lung injury. Altex, 37(4), 545-560. doi:10.14573/altex.2001271en_US
dc.identifier.issn1868-596X
dc.identifier.pmid32449787
dc.identifier.doi10.14573/altex.2001271
dc.identifier.urihttp://hdl.handle.net/2336/621675
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Downloaden_US
dc.description.abstractAzithromycin (AZM) is a broad-spectrum antibiotic widely used to treat infections. AZM also has been shown to have anti-inflammatory and immunomodulatory functions unrelated to its antibacterial activity that contribute to the effectiveness of this drug in chronic respiratory diseases. The mechanisms behind these beneficial effects are not yet fully elucidated. We have previously shown that AZM enhances barrier integrity of bronchial epithelial cells and directs them towards epidermal differentiation. In this study, we analyzed the effect of AZM pre-treatment of human bronchial and alveolar derived cell lines on mechanical stress in a cyclical pressure air-liquid interface device (CPAD) that models the disruption of the epithelial barrier with increased inflammatory response in lung tissue, which is associated with ventilator-induced lung injury (VILI). Immunostaining and electron microscopy showed that barrier integrity of the epithelium was compromised by cyclically stressing the cells but maintained when cells had been pre-treated with AZM. Lamellar body formation was revealed in AZM pre-treated cells, possibly further supporting the barrier-enhancing effects. RNA sequencing showed that the inflammatory response was attenuated by AZM treatment before cyclical stress. YKL-40, an emerging inflammatory marker, increased both due to cyclical stress and upon AZM treatment. These data confirm the usefulness of the CPAD to model ventilator-induced lung injury and suggest that AZM has barrier protective and immunomodulatory effects, attenuating the inflammatory response during mechanical stress, and might therefore be lung protective during mechanical ventilation. The model could be used to assess further drug candidates that influence barrier integrity and modulate inflammatory response. Keywords: YKL-40; airway epithelium; azithromycin; immunomodulation; ventilator-induced lung injury.en_US
dc.description.sponsorshipIcelandic Research Council Landspitali University Hospital science funden_US
dc.language.isoenen_US
dc.publisherSpektrum Akademischer Verlagen_US
dc.relation.urlhttps://www.altex.org/index.php/altex/article/view/1525en_US
dc.subjectYKL-40en_US
dc.subjectairway epitheliumen_US
dc.subjectazithromycinen_US
dc.subjectimmunomodulationen_US
dc.subjectventilator-induced lung injuryen_US
dc.subjectSýklalyfen_US
dc.subjectÖndunarvélaren_US
dc.subjectLunguen_US
dc.subject.meshVentilator-Induced Lung Injuryen_US
dc.subject.meshAzithromycinen_US
dc.titleAzithromycin has lung barrier protective effects in a cell model mimicking ventilator-induced lung injury.en_US
dc.typeArticleen_US
dc.contributor.department1Stem Cell Research Unit, BioMedical Center, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 2Department of Laboratory Hematology, Landspitali-University Hospital, Reykjavík, Iceland. 3Life and Environmental Sciences, BioMedical Center, University of Iceland, Reykjavík, Iceland. 4EpiEndo Pharmaceuticals, Reykjavík, Iceland. 5Sackler Institute of Pulmonary Pharmacology, King's College London, London, UK. 6Landspitali-University Hospital, Intensive Care Unit, Reykjavík, Iceland.en_US
dc.identifier.journalALTEXen_US
dc.rights.accessOpen Access - Opinn aðganguren_US
dc.departmentcodeAAA12
dc.source.journaltitleALTEX
dc.source.volume37
dc.source.issue4
dc.source.beginpage545
dc.source.endpage560
refterms.dateFOA2021-03-01T10:53:32Z
dc.source.countryGermany


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