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.
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Authors | Manuel Mata, Isidoro Martinez, Jose A Melero, Herman Tenor, Julio Cortijo |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 7
Pg. e69670
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23936072
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aminopyridines
- Antioxidants
- Benzamides
- Biomarkers
- CLCA1 protein, human
- Chloride Channels
- Cyclopropanes
- Cytokines
- DNAI1 protein, human
- FOXJ1 protein, human
- Forkhead Transcription Factors
- MUC5AC protein, human
- Mucin 5AC
- RNA, Messenger
- Reactive Oxygen Species
- Tubulin
- Roflumilast
- Axonemal Dyneins
- roflumilast N-oxide
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Topics |
- Aminopyridines
(pharmacology, therapeutic use)
- Antioxidants
(metabolism)
- Axonemal Dyneins
(metabolism)
- Benzamides
(pharmacology, therapeutic use)
- Biomarkers
(metabolism)
- Bronchi
(pathology)
- Cell Count
- Cell Differentiation
(drug effects)
- Chloride Channels
(genetics, metabolism)
- Cilia
(drug effects, metabolism)
- Cyclopropanes
(pharmacology, therapeutic use)
- Cytokines
(metabolism)
- Epithelial Cells
(drug effects, pathology, virology)
- Forkhead Transcription Factors
(metabolism)
- Goblet Cells
(drug effects, pathology)
- Humans
- Metaplasia
- Mucin 5AC
(genetics, metabolism)
- Oxidative Stress
(drug effects)
- RNA, Messenger
(genetics, metabolism)
- Reactive Oxygen Species
(metabolism)
- Respiratory Syncytial Virus Infections
(drug therapy, virology)
- Respiratory Syncytial Viruses
(drug effects, physiology)
- Tubulin
(metabolism)
- Viral Load
(drug effects)
- Virus Replication
(drug effects)
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