Roflumilast Inhibits Respiratory Syncytial Virus Infection in Human Differentiated Bronchial Epithelial CellsReportar como inadecuado




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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.



Autor: Manuel Mata , Isidoro Martinez, Jose A. Melero, Herman Tenor, Julio Cortijo

Fuente: http://plos.srce.hr/



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