title: 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.
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.
authors.affiliation: Institute of Medical Virology, Johann Wolfgang Goethe-University Frankfurt, Paul-Ehrlich-Strasse 40, 60596 Frankfurt am Main, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Geiler
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Patrizia
authors.initials: P
authors.lastname: Naczk
authors.forename: Anke
authors.initials: A
authors.lastname: Leutz
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
authors.forename: Hans-Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000502:physiology; D007251:Influenza, Human / Q000378:metabolism / Q000517:prevention & control; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D018836:Inflammation Mediators; D000111:Acetylcysteine