Investigation of Kampo medicine mechanism against the infection via type 1 interferon producing cells

我们已经发现，汉方药物juzentaihoto作用于干扰素基因表达信号通路，控制干扰素的产生。为了进一步研究干扰素的产生机制，我们尝试对大肠中产生干扰素的细胞和Kampo药物的作用机制进行了鉴定。通过对Toll样受体4(TLR-4)和myd 88基因敲除小鼠的分析，通过TLR-4依赖和MyD88非依赖的信号通路来观察juzentaihoto的作用机制。在MyD88基因敲除小鼠中，IRF-7等1型干扰素相关基因表达上调。在无菌小鼠身上也观察到了这种升高。在所有这些小鼠中，某些类型的单核细胞起着重要作用。这些单核细胞还没有鉴定出来。为了探讨菊泽泰和在流感病毒感染中的作用，我们将其应用于C57BL/6小鼠。然而，Hochuekkito对流感病毒的保护作用强于Juzentaihoto。我们研究了Hochuekkito抗流感病毒的作用机制，发现防御素4在体内升高。在体外实验中，Hochuekkito抑制了流感病毒与MDCK细胞的黏附。这些机制可能解释了Hochuekkito抗流感病毒的有效性。

We have found the Kampo medicine, juzentaihoto acts on interferon(IFN) gene expression signal pathway and controls the IFN production. For the further investigation of the mechanisms of IFN production, we have tried to identify the IFN producing cells in the large intestine and Kampo drugs action mechanisms. Analysis of toll like receptor 4(TLR-4) and MyD 88 knock-out mice, the mechanism of action of juzentaihoto was observed via TLR-4 dependent and MyD88 independent signal pathway. In the MyD88 knock-out mouse, type 1 IFN related genes, like IRF-7 was elevated. This elevation was also observed in the germ free mouse. Among all these mice, certain type of monocytes played an important role. These monocytes have not identified yet. In order to investigate the role of juzentaihoto on the influenza infection, we applied juzentaihoto to C57BL/6 mouse. However the protective action against influenza virus was stronger with hochuekkito than with juzentaihoto. We investigated the mechanism of action of hochuekkito against the influenza virus and found the defensin 4 was elevated in vivo. In vitro experiments, adhesion of influenza virus to MDCK cells was inhibited by hochuekkito. These mechanism may explain the effectiveness of hochuekkito against the influenza virus.