6533b821fe1ef96bd127af42

RESEARCH PRODUCT

Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine.

Carmen CardaJosé A. MeleroJosé A. MeleroMiguel ArmengotIrene SarrionJulio CortijoManuel De La MataIsidoro MartínezIsidoro Martínez

subject

Viral DiseasesPulmonologyChronic Obstructive Pulmonary Diseaseslcsh:MedicineMucin 5ACVirus ReplicationAcetylcysteinePulmonary Disease Chronic ObstructiveTubulinRespiratory systemlcsh:ScienceCells CulturedMultidisciplinaryInterleukin-13Microscopy VideoCell DifferentiationForkhead Transcription FactorsFree Radical Scavengersrespiratory systemHost-Pathogen InteractionLower Respiratory Tract InfectionsInfectious Diseasesmedicine.anatomical_structureInterleukin 13Medicinemedicine.symptomResearch Articlemedicine.drugDrugs and DevicesInflammationBronchiRespiratory Syncytial Virus InfectionsBiologyMicrobiologyAntiviral AgentsUpper Respiratory Tract InfectionsmedicineHumansCiliaBiologyInflammationRespiratory Syncytial Virus InfectionA549 cellMucinlcsh:RImmunityEpithelial CellsAxonemal DyneinsEpitheliumAcetylcysteineGene Expression RegulationRespiratory Syncytial Virus HumanRespiratory InfectionsImmunologyRespiratory epitheliumlcsh:Q

description

Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H(2)O(2) levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD. This work was supported by grants SAF2005-00669/SAF2008-03113 (JC), PI10/02294 (MM), and CIBERES (CB06/06/0027) from the Ministry of Science and Innovation and the Health Institute ‘Carlos III’ of the Spanish government as well as research grants from regional government (GV2007/287 and AP073/10, Generalitat Valenciana). Sí

yearjournalcountryeditionlanguage
2012-10-01PLoS ONE
10.1371/journal.pone.0048037http://europepmc.org/articles/PMC3485262?pdf=render