Abstract
Background:
Viral infections often trigger the onset or worsening of glomerular diseases, but the details of this mechanism are unclear. Fractalkine/CX3CL1 (Fkn) is a chemokine that induces the chemotaxis and activation of cells expressing its receptor, CX3CR1. To examine the involvement of glomerular Fkn expression in the development of glomerulonephritis after viral infection, we conducted experimental studies using human mesangial cells (MCs) in culture.
Methods:
We examined the effect of polyinosinic-polycytidylic acid (poly IC), an authentic viral double-stranded RNA, on Fkn expression in MCs to investigate the involvement of Fkn in the antiviral reaction of MCs. Fkn mRNA and protein were analyzed using real-time PCR and enzyme-linked immunosorbent assay. Also, an immunofluorescent study to examine mesangial Fkn expression in biopsy specimens obtained from patients with glomerulonephritis was conducted.
Results:
Poly IC–induced Fkn expression in MCs in both a time- and dose-dependent manner, and RNA interference (RNAi) against Toll-like receptor 3 (TLR3) or interferon regulatory factor 3 (IRF3) inhibited poly IC–induced Fkn expression. Significant glomerular Fkn expression was observed in biopsy specimens from patients with immunoglobulin A nephropathy and purpura nephritis, with increasing severity of glomerular inflammation.
Conclusion:
The TLR3/IRF3/Fkn signaling pathway may, at least in part, mediate immune and inflammatory responses against viral infection in MCs.
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The authors thank Kumiko Munakata, Miho Ono, Michiko Nakata, and Ai Yamamoto for their help.
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Aizawa-Yashiro, T., Imaizumi, T., Tsuruga, K. et al. Glomerular expression of fractalkine is induced by polyinosinic-polycytidylic acid in human mesangial cells: possible involvement of fractalkine after viral infection. Pediatr Res 73, 180–186 (2013). https://doi.org/10.1038/pr.2012.165
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DOI: https://doi.org/10.1038/pr.2012.165
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