N-acetyl-L-cysteine (NAC) Inhibits Virus Replication and Expression of Pro-Inflammatory Molecules in A549 Cells Infected With Highly Pathogenic H5N1 Influenza A Virus

Biochem Pharmacol. 2010 Feb 1;79(3):413-20. doi: 10.1016/j.bcp.2009.08.025. Epub 2009 Sep 2.

Abstract

The antioxidant N-acetyl-L-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on virus replication, virus-induced pro-inflammatory responses and virus-induced apoptosis were investigated in H5N1-infected lung epithelial (A549) cells. NAC at concentrations ranging from 5 to 15 mM reduced H5N1-induced cytopathogenic effects (CPEs), virus-induced apoptosis and infectious viral yields 24 h post-infection. NAC also decreased the production of pro-inflammatory molecules (CXCL8, CXCL10, CCL5 and interleukin-6 (IL-6)) in H5N1-infected A549 cells and reduced monocyte migration towards supernatants of H5N1-infected A549 cells. The antiviral and anti-inflammatory mechanisms of NAC included inhibition of activation of oxidant sensitive pathways including transcription factor NF-kappaB and mitogen activated protein kinase p38. Pharmacological inhibitors of NF-kappaB (BAY 11-7085) or p38 (SB203580) exerted similar effects like those determined for NAC in H5N1-infected cells. The combination of BAY 11-7085 and SB203580 resulted in increased inhibitory effects on virus replication and production of pro-inflammatory molecules relative to either single treatment. NAC inhibits H5N1 replication and H5N1-induced production of pro-inflammatory molecules. Therefore, antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Acetylcysteine / therapeutic use
  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Cell Line, Tumor
  • Cells, Cultured
  • Chlorocebus aethiops
  • Gene Expression Regulation, Viral / drug effects*
  • Gene Expression Regulation, Viral / physiology
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Influenza A Virus, H5N1 Subtype / drug effects*
  • Influenza A Virus, H5N1 Subtype / physiology
  • Influenza, Human / metabolism
  • Influenza, Human / prevention & control
  • Vero Cells
  • Virus Replication / drug effects*
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • Inflammation Mediators
  • Acetylcysteine