title: TNF-alpha and IFN-alpha enhance influenza-A-virus-induced chemokine gene expression in human A549 lung epithelial cells.
abstract: Lung epithelial cells are the primary cellular targets for respiratory virus pathogens such as influenza and parainfluenza viruses. Here, we have analyzed influenza A, influenza B and Sendai virus-induced chemokine response in human A549 lung epithelial cells. Influenza virus infection resulted in low CCL2/MCP-1, CCL5/RANTES, CXCL8/IL-8 and CXCL10/IP-10 production at late times of infection. However, when cells were pretreated with TNF-alpha or IFN-alpha, influenza-A-virus-induced chemokine production was greatly enhanced. Cytokine pretreatment resulted in enhanced expression of RIG-I, IKKepsilon, interferon regulatory factor (IRF)1, IRF7 and p50 proteins. Most importantly, influenza-A-virus-induced DNA binding of IRF1, IRF3, IRF7 and NF-kappaB onto CXCL10 ISRE and NF-kappaB elements, respectively, was markedly enhanced in cytokine-pretreated cells. Our results suggest that IFN-alpha and TNF-alpha have a significant role in priming epithelial cells for higher cytokine and chemokine production in influenza A virus infection.
authors.affiliation: Department of Viral Diseases and Immunology, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. ville.veckman@ktl.fi
authors.forename: Ville
authors.initials: V
authors.lastname: Veckman
authors.forename: Pamela
authors.initials: P
authors.lastname: Osterlund
authors.forename: Riku
authors.initials: R
authors.lastname: Fagerlund
authors.forename: Krister
authors.initials: K
authors.lastname: Melén
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Julkunen
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000821:virology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D016898:Interferon-alpha / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D029082:Sendai virus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D018925:Chemokines; D016898:Interferon-alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha