N-Acetyl-l-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with Respiratory Syncytial Virus (RSV)

Manuel Mata (1, 2, 3) , Esteban Morcillo (2, 3) , Concepcion Gimeno (3, 4) , Julio Cortijo (2, 3)

1 research Foundation of the University General Hospital of Valencia
2 Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias
3 University of Valencia
4 University General Hospital of Valencia

64% of Chronic Obstructive Pulmonary Disease (COPD) exacerbations are caused by respiratory infections including influenza (strains A and B) and Respiratory Syncytial Virus (RSV). They affect the airway epithelium increasing inflammatory and apoptosis events through mechanisms involving ROS generation, and induce the release of mucins from epithelial cells that are involved in the deterioration of the patient's health during the course of the disease. The antioxidant NAC has probed useful in the management of COPD reducing symptoms, exacerbations and accelerated lung function decline. It has been shown to inhibit influenza virus replication and to diminish the release of inflammatory and apoptotic mediators during virus infection. The main objective of this study is to analyze the effects of NAC in modulating MUC5AC over-expression and release in an in vitro infection model of alveolar type II A549 cells infected with influenza (strains A and B) and RSV. We have also analyzed virus replication and different pro-inflammatory responses. Our results indicate a significant induction of MUC5AC, IL8, IL6 and TNF-alpha that is strongly inhibited by NAC at the expression and at the release level. It also decreased the intracellular HO concentration and restored the intracellular total thiol contents. Mechanisms of NAC included inhibition of NF-κB translocation to the cellular nucleus and phosphorylation of MAPK p38. NAC also inhibited replication of the three viruses under study. This work supports the use of antioxidants in order to ameliorate the inflammatory effects of different viral infections during COPD exacerbations.

Mots clés: Influenza; RSV; COPD; NAC; MUC5AC

Domaines: Pharmacologie

Manuel Mata, Esteban Morcillo, Concepcion Gimeno, Julio Cortijo. N-Acetyl-l-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with Respiratory Syncytial Virus (RSV). Biochemical Pharmacology, 2011, 82 (5), pp.548. ⟨10.1016/j.bcp.2011.05.014⟩. ⟨hal-00721646⟩