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dc.contributor.authorMata, Manuel
dc.contributor.authorMartinez, Isidoro 
dc.contributor.authorMelero, Jose Antonio 
dc.contributor.authorTenor, Herman
dc.contributor.authorCortijo, Julio
dc.date.accessioned2018-12-27T11:17:08Z
dc.date.available2018-12-27T11:17:08Z
dc.date.issued2013-07-23
dc.identifier.citationPLoS One. 2013 Jul 23;8(7):e69670es_ES
dc.identifier.issn1932-6203es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6964
dc.description.abstractRespiratory syncytial virus (RSV) causes acute exacerbations in COPD and asthma. RSV infects bronchial epithelial cells (HBE) that trigger RSV associated lung pathology. This study explores whether the phosphodiesterase 4 (PDE4) inhibitor Roflumilast N-oxide (RNO), alters RSV infection of well-differentiated HBE (WD-HBE) in vitro. WD-HBE were RSV infected in the presence or absence of RNO (0.1-100 nM). Viral infection (staining of F and G proteins, nucleoprotein RNA level), mRNA of ICAM-1, ciliated cell markers (digital high speed videomicroscopy, β-tubulin immunofluorescence, Foxj1 and Dnai2 mRNA), Goblet cells (PAS), mRNA of MUC5AC and CLCA1, mRNA and protein level of IL-13, IL-6, IL-8, TNFα, formation of H2O2 and the anti-oxidative armamentarium (mRNA of Nrf2, HO-1, GPx; total antioxidant capacity (TAC) were measured at day 10 or 15 post infection. RNO inhibited RSV infection of WD-HBE, prevented the loss of ciliated cells and markers, reduced the increase of MUC5AC and CLCA1 and inhibited the increase of IL-13, IL-6, IL-8, TNFα and ICAM-1. Additionally RNO reversed the reduction of Nrf2, HO-1 and GPx mRNA levels and consequently restored the TAC and reduced the H2O2 formation. RNO inhibits RSV infection of WD-HBE cultures and mitigates the cytopathological changes associated to this virus.es_ES
dc.description.sponsorshipThis work was supported by grants SAF2008-03113/SAF2011-26443 (JC), PI10/02294 (MM), and CIBERES (CB06/06/0027) from the Ministry of Economy and Competitiveness and the Health Institute ‘Carlos III’ of the Spanish Government and research grants from Regional Government (GV2007/287 and AP073/10, from GeneralitatValenciana). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptes_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAminopyridines es_ES
dc.subject.meshAntioxidants es_ES
dc.subject.meshAxonemal Dyneins es_ES
dc.subject.meshBenzamides es_ES
dc.subject.meshBiomarkers es_ES
dc.subject.meshBronchi es_ES
dc.subject.meshCell Count es_ES
dc.subject.meshCell Differentiation es_ES
dc.subject.meshChloride Channels es_ES
dc.subject.meshCilia es_ES
dc.subject.meshCyclopropanes es_ES
dc.subject.meshCytokines es_ES
dc.subject.meshEpithelial Cells es_ES
dc.subject.meshForkhead Transcription Factors es_ES
dc.subject.meshGoblet Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMetaplasia es_ES
dc.subject.meshMucin 5AC es_ES
dc.subject.meshOxidative Stress es_ES
dc.subject.meshRNA, Messenger es_ES
dc.subject.meshReactive Oxygen Species es_ES
dc.subject.meshRespiratory Syncytial Virus Infections es_ES
dc.subject.meshRespiratory Syncytial Viruses es_ES
dc.subject.meshTubulin es_ES
dc.subject.meshViral Load es_ES
dc.subject.meshVirus Replication es_ES
dc.titleRoflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cellses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID23936072es_ES
dc.format.volume8es_ES
dc.format.number7es_ES
dc.format.pagee69670es_ES
dc.identifier.doi10.1371/journal.pone.0069670es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderGeneralitat Valenciana (España) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1932-6203es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pone.0069670es_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CB06/06/0027es_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/MICINN//SAF2011-26443/ES/MODIFICACION FARMACOLOGICA DEL REMODELADO Y EPOC INDUCIDOS POR EL HUMO DEL TABACO: VISION EN MODELOS ANIMALES Y HUMANOS/ 
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/MICINN//SAF2008-03113/ES/ESTUDIO FARMACOLOGICO DE LA ACTIVIDAD ANTIINFLAMATORIA DE INHIBIDORES FOSFODIESTERASA 4, EN CELULAS EPITELIALES DE VIA AEREA HUMANA IN VITRO, FRENTE AL HUMO DEL TABACO Y %2FO INFECCIONES POR VIRUS/ 
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigación en salud (AES 2010) (2010)/PI10/02294


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Atribución 4.0 Internacional
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