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

我们发现汉方药juzentaihoto作用于干扰素（IFN）基因表达信号通路，控制IFN的产生。为了进一步研究IFN的产生机制，我们试图鉴定大肠中的IFN产生细胞和汉方药物的作用机制。通过对TLR-4和MyD 88基因敲除小鼠的分析，探讨了juzentaihoto通过TLR-4依赖性和MyD 88非依赖性信号通路的作用机制。在MyD 88敲除小鼠中，1型IFN相关基因如IRF-7升高。在无菌小鼠中也观察到这种升高。在所有这些小鼠中，某些类型的单核细胞发挥了重要作用。这些单核细胞尚未鉴定。为了研究浓缩大花汤对流感病毒感染的作用，我们将浓缩大花汤应用于C57 BL/6小鼠。然而，对流感病毒的保护作用与hochuekkito比juzentaihoto强。我们研究了hochuekkito对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抑制流感病毒对MDCK细胞的粘附。这些机制可以解释hochuekkito对流感病毒的有效性。

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.