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Japanese encephalitis virus up-regulates expression of macrophage migration inhibitory factor (MIF) mRNA in the mouse
1Central Research Institute, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract:
Macrophage migration inhibitory factor (MIF) is known as a proinflammatory cytokine, glucocorticoid-induced immunomodulator, and pituitary hormone, and contributes to broad-spectrum immune and inflammatory response. To investigate the expression of MIF in the central nervous system in an event of viral infection, we evaluated MIF mRNA expression in the mouse brain infected with Japanese encephalitis virus (JEV). In situ hybridization revealed that MIF mRNA expression was significantly up-regulated in the whole brain by intracranial JEV inoculation at 2 days post-inoculation (d.p.i.). Neurons as well as glial cells expressed MIF transcripts in which some of these cells were co-labeled by double staining for JEV antigens and MIF mRNA. At 4 d.p.i., when typical symptoms of encephalitis were observed, JEV antigen-positive cells were much increased in parallel with enhanced MIF mRNA, consistent with the results of Northern blot analysis. Reverse transcription-polymerase chain reaction showed that MIF mRNA was minimally changed at 1 d.p.i. in comparison with that at 0 d.p.i., but markedly up-regulated after 2 d.p.i. and sustained up to 4 d.p.i. On the other hand, a significant increase of tumor necrosis factor (TNF)-alpha mRNA was observed after only 3 d.p.i. These data suggest the possibility that MIF is involved in virus-induced encephalitis with regard to not only immune responses in the early stage, but also the exacerbation of inflammation in concert with TNF-alpha in the late stages. This is the first evidence demonstrating that MIF is up-regulated in the case of virus-induced encephalitis, which should contribute to the further understanding of the pathological mechanism of JEV-induced encephalitis.
Insights
Macrophage migration inhibitory factor (MIF) is upregulated in the mouse brain during Japanese encephalitis virus (JEV) infection. This suggests MIF plays a role in early immune responses and late-stage inflammation in JEV-induced encephalitis.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in immune responses.
- Its role in the central nervous system during viral infections is not well understood.
Purpose of the Study:
- To investigate the expression of MIF in the mouse brain following Japanese encephalitis virus (JEV) infection.
- To determine MIF's potential involvement in the pathogenesis of JEV-induced encephalitis.
Main Methods:
- Intracranial inoculation of JEV in mice.
- In situ hybridization and Northern blot analysis to assess MIF mRNA expression.
- Reverse transcription-polymerase chain reaction (RT-PCR) to quantify MIF and TNF-alpha mRNA.
- Double staining for JEV antigens and MIF mRNA.
Main Results:
- MIF mRNA expression was significantly upregulated in the whole brain by 2 days post-inoculation (d.p.i.) and sustained up to 4 d.p.i.
- MIF transcripts were detected in neurons and glial cells, with some co-localization with JEV antigens.
- Tumor necrosis factor (TNF)-alpha mRNA increased significantly at 3 d.p.i.
Conclusions:
- MIF is upregulated in the brain during JEV infection, indicating its involvement in the early immune response.
- MIF may contribute to the exacerbation of inflammation in JEV-induced encephalitis, potentially in conjunction with TNF-alpha.
- This study provides the first evidence of MIF upregulation in virus-induced encephalitis, advancing understanding of JEV pathogenesis.