Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6964
Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells
Mata, Manuel | Martinez, Isidoro ISCIII | Melero, Jose Antonio ISCIII | Tenor, Herman | Cortijo, Julio
PLoS One. 2013 Jul 23;8(7):e69670
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.
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
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