Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.

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-diffe...

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Autores principales: Manuel Mata, Isidoro Martinez, Jose A Melero, Herman Tenor, Julio Cortijo
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:eeffae9a83494ce4973afe86641607342021-11-18T09:03:15ZRoflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.1932-620310.1371/journal.pone.0069670https://doaj.org/article/eeffae9a83494ce4973afe86641607342013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936072/?tool=EBIhttps://doaj.org/toc/1932-6203Respiratory 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.Manuel MataIsidoro MartinezJose A MeleroHerman TenorJulio CortijoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69670 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Manuel Mata
Isidoro Martinez
Jose A Melero
Herman Tenor
Julio Cortijo
Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
description 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.
format article
author Manuel Mata
Isidoro Martinez
Jose A Melero
Herman Tenor
Julio Cortijo
author_facet Manuel Mata
Isidoro Martinez
Jose A Melero
Herman Tenor
Julio Cortijo
author_sort Manuel Mata
title Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
title_short Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
title_full Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
title_fullStr Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
title_full_unstemmed Roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
title_sort roflumilast inhibits respiratory syncytial virus infection in human differentiated bronchial epithelial cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/eeffae9a83494ce4973afe8664160734
work_keys_str_mv AT manuelmata roflumilastinhibitsrespiratorysyncytialvirusinfectioninhumandifferentiatedbronchialepithelialcells
AT isidoromartinez roflumilastinhibitsrespiratorysyncytialvirusinfectioninhumandifferentiatedbronchialepithelialcells
AT joseamelero roflumilastinhibitsrespiratorysyncytialvirusinfectioninhumandifferentiatedbronchialepithelialcells
AT hermantenor roflumilastinhibitsrespiratorysyncytialvirusinfectioninhumandifferentiatedbronchialepithelialcells
AT juliocortijo roflumilastinhibitsrespiratorysyncytialvirusinfectioninhumandifferentiatedbronchialepithelialcells
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