Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/6964
Título
Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells
Autor(es)
Mata, Manuel | Martinez, Isidoro ISCIII | Melero, Jose Antonio ISCIII | Tenor, Herman | Cortijo, Julio
Fecha de publicación
2013-07-23
Cita
PLoS One. 2013 Jul 23;8(7):e69670
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Aminopyridines | Antioxidants | Axonemal Dyneins | Benzamides | Biomarkers | Bronchi | Cell Count | Cell Differentiation | Chloride Channels | Cilia | Cyclopropanes | Cytokines | Epithelial Cells | Forkhead Transcription Factors | Goblet Cells | Humans | Metaplasia | Mucin 5AC | Oxidative Stress | RNA, Messenger | Reactive Oxygen Species | Respiratory Syncytial Virus Infections | Respiratory Syncytial Viruses | Tubulin | Viral Load | Virus Replication
Versión en línea
DOI
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