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)

Biochem Pharmacol. 2011 Sep 1;82(5):548-55. doi: 10.1016/j.bcp.2011.05.014. Epub 2011 May 25.


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 proved 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 H(2)O(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Acetylcysteine / therapeutic use
  • Cell Line
  • Humans
  • Inflammation Mediators / metabolism*
  • Influenza A virus / drug effects
  • Influenza A virus / physiology
  • Influenza B virus / drug effects
  • Influenza B virus / physiology
  • Mucin 5AC / antagonists & inhibitors*
  • Mucin 5AC / biosynthesis
  • NF-kappa B / metabolism
  • Phosphorylation
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / virology
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Respiratory Syncytial Viruses / drug effects
  • Respiratory Syncytial Viruses / physiology
  • Virus Replication / drug effects*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Inflammation Mediators
  • MUC5AC protein, human
  • Mucin 5AC
  • NF-kappa B
  • p38 Mitogen-Activated Protein Kinases
  • Acetylcysteine