Influenza A and Sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages

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Abstract

Chemokines regulate leukocyte traffic and extravasation into the site of inflammation. Here we show that influenza A- or Sendai virus-infected human macrophages produce MIP-1α, MIP-1β, RANTES, MCP-1, MCP-3, MIP-3α, IP-10, and IL-8, whereas no upregulation of MIP-3β, eotaxin, or MDC production was detected. Influenza A virus was a better inducer of MCP-1 and MCP-3 production than Sendai virus, whereas MIP-1α, MIP-1β, RANTES, MIP-3α and IL-8 were induced preferentially by Sendai virus. Infection in the presence of protein synthesis inhibitor indicated that ongoing protein synthesis was required for influenza A virus-induced expression of MCP-1, MCP-3, and IP-10 genes, whereas Sendai virus-induced chemokine mRNA expression took place in the absence of de novo protein synthesis. Neutralization of virus-induced IFN-α/β resulted in downregulation of virus-induced IP-10, MCP-1, and MCP-3 mRNA expression. IFN-α or IFN-γ were found to directly enhance MCP-1, MCP-3, and IP-10 mRNA expression. Both influenza A and Sendai viruses similarly activated transcription factor NF-κB. In contrast to NF-κB, IRFs and STATs, the other transcription factors involved in the regulation of chemokine gene expression, were differentially activated by these viruses. Influenza A virus more efficiently activated ISGF3 complex formation and Stat1 DNA-binding compared to Sendai virus, which in turn was a more potent activator of IRF-1. Our results show that during viral infections macrophages predominantly produce monocyte and Th1 cell attracting chemokines. Furthermore, virus-induced IFN-α/β enhanced chemokine gene expression in macrophages emphasizing the role of IFN-α/β in the development of Th1 immune responses. (C) 2000 Academic Press.

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Matikainen, S., Pirhonen, J., Miettinen, M., Lehtonen, A., Govenius-Vintola, C., Sareneva, T., & Julkunen, I. (2000). Influenza A and Sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. Virology, 276(1), 138–147. https://doi.org/10.1006/viro.2000.0542

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