TNF-alpha and IFN-alpha enhance influenza-A-virus-induced chemokine gene expression in human A549 lung epithelial cells.
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.
Veckman
Ville
V
Department of Viral Diseases and Immunology, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. ville.veckman@ktl.fi
Osterlund
Pamela
P
Fagerlund
Riku
R
Melén
Krister
K
Matikainen
Sampsa
S
Julkunen
Ilkka
I
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*
D018925:Chemokines; D016898:Interferon-alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha