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dc.contributor.author | Mata, Manuel | |
dc.contributor.author | Martinez, Isidoro | |
dc.contributor.author | Melero, Jose Antonio | |
dc.contributor.author | Tenor, Herman | |
dc.contributor.author | Cortijo, Julio | |
dc.date.accessioned | 2018-12-27T11:17:08Z | |
dc.date.available | 2018-12-27T11:17:08Z | |
dc.date.issued | 2013-07-23 | |
dc.identifier.citation | PLoS One. 2013 Jul 23;8(7):e69670 | es_ES |
dc.identifier.issn | 1932-6203 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6964 | |
dc.description.abstract | Respiratory 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.sponsorship | This 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 manuscript | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library of Science (PLOS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Aminopyridines | es_ES |
dc.subject.mesh | Antioxidants | es_ES |
dc.subject.mesh | Axonemal Dyneins | es_ES |
dc.subject.mesh | Benzamides | es_ES |
dc.subject.mesh | Biomarkers | es_ES |
dc.subject.mesh | Bronchi | es_ES |
dc.subject.mesh | Cell Count | es_ES |
dc.subject.mesh | Cell Differentiation | es_ES |
dc.subject.mesh | Chloride Channels | es_ES |
dc.subject.mesh | Cilia | es_ES |
dc.subject.mesh | Cyclopropanes | es_ES |
dc.subject.mesh | Cytokines | es_ES |
dc.subject.mesh | Epithelial Cells | es_ES |
dc.subject.mesh | Forkhead Transcription Factors | es_ES |
dc.subject.mesh | Goblet Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Metaplasia | es_ES |
dc.subject.mesh | Mucin 5AC | es_ES |
dc.subject.mesh | Oxidative Stress | es_ES |
dc.subject.mesh | RNA, Messenger | es_ES |
dc.subject.mesh | Reactive Oxygen Species | es_ES |
dc.subject.mesh | Respiratory Syncytial Virus Infections | es_ES |
dc.subject.mesh | Respiratory Syncytial Viruses | es_ES |
dc.subject.mesh | Tubulin | es_ES |
dc.subject.mesh | Viral Load | es_ES |
dc.subject.mesh | Virus Replication | es_ES |
dc.title | Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 23936072 | es_ES |
dc.format.volume | 8 | es_ES |
dc.format.number | 7 | es_ES |
dc.format.page | e69670 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0069670 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Generalitat Valenciana (España) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1932-6203 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1371/journal.pone.0069670 | es_ES |
dc.identifier.journal | PloS one | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/CB06/06/0027 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info: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.projectFECYT | info: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.projectFIS | info:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigación en salud (AES 2010) (2010)/PI10/02294 |