Abstract
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 H2O2 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.
Highlights
Human respiratory syncytial virus (RSV; genus Pneumovirus, family Paramixoviridae) is an important pathogen that causes serious infection in people of all ages, including children, healthy and sick adults, and elderly individuals [1,2]
The main objective of this study was to analyze the effects of NAC in an in vitro model of RSV infection developed on air–liquid interface (ALI)-differentiated normal human bronchial epithelial cells (NHBECs)
We studied the effects of this drug on viral replication, ciliary activity, ciliagenesis, and mucin production as well as its antioxidant effects by measuring the total antioxidant status (TAS), the intracellular H2O2 and glutathione levels and the expression of nuclear receptor factor 2 (Nrf2), heme oxygenase 1 (HO1), and ICAM1
Summary
Human respiratory syncytial virus (RSV; genus Pneumovirus, family Paramixoviridae) is an important pathogen that causes serious infection in people of all ages, including children, healthy and sick adults, and elderly individuals [1,2]. This virus results in persistent infection, leading to chronic inflammation through mechanisms involving continuous stimulation of the immune system [3,4,5]. During COPD exacerbations, an increase occurs in sputum volume, which in the airways is the result of a balance between the ciliary beat of epithelial cells and mucin production [8]. ROIs are necessary for RSV infection and are involved in the inflammatory response of host cells [16]
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