Microarray analysis on germfree mice elucidates the primary target of a traditional Japanese medicine juzentaihoto: acceleration of IFN-α response via affecting the ISGF3-IRF7 signaling cascade

BMC Genomics

Research Article

Kaori Munakata¹  Kiyoe Takashima¹  Kenji Watanabe¹  Masahiro Yamamoto²  Kyoji Hioki³  Yasuyuki Ohnishi³  Naoko Asano⁴  Akihito Mase⁴  Mitsue Nishiyama⁴ 

[1] Center for Kampo Medicine, Keio University School of Medicine, Tokyo, Japan;Center for Kampo Medicine, Keio University School of Medicine, Tokyo, Japan;Tsumura Research Laboratories, Tsumura & Co., 300-1192, Ami, Ibaraki, Japan;Central Institute for Experimental Animals, 1430 Nogawa, Miyamae-ku, 216-0001, Kawasaki, Kanagawa, Japan;Tsumura Research Laboratories, Tsumura & Co., 300-1192, Ami, Ibaraki, Japan;

关键词: Large Intestine;    Chronic Fatigue Syndrome;    Interferon Regulatory Factor;    Imiquimod;    Intestinal Microflora;   

DOI  :  10.1186/1471-2164-13-30

 received in 2011-09-22, accepted in 2012-01-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe traditional Japanese medicine juzentaihoto (JTX) is a pharmaceutical grade multi-herbal medicine widely used for the prevention of cancer metastasis and infection in immuno-compromized patients in Japan. The effect of JTX has been supposed to be intimately affected by the immunological properties of host and enteric microflora. The influence of JTX on the gene expression profile in the large and small intestines was investigated by microarray analyses using mice of different strains with or without enteric microflora.ResultsIn all types of mice, including germfree (GF) animals, the genes most affected by two-week oral JTX treatment were the type 1 interferon (IFN)-related genes including Stat1, Isgf3g and Irf7, which play a critical role in the feedback loop of IFN-α production cascade. In IQI specific pathogen free (SPF) mice JTX increased the steady state level of the expression of IFN-related genes, but had the opposite effect in IQI GF and BALB/c SPF mice. Promoter analysis suggests that tandem repeated $IRFF (the promoter sequences for interferon regulatory factors) may be a primary target for JTX action. Pre-treatment of JTX accelerated the effects of an oral IFN "inducer" 2-amino-5-bromo-6-methyl-4-pyrimidinol (ABMP) (up-regulation of IFN-α production in IQI strain and down-regulation in BALB/c mice), which is in good accordance with the effect of JTX on gene expression of type 1 IFN-related genes.ConclusionsMicroarray analysis revealed that the target of JTX might be the transcription machinery regulating the steady-state level of genes involved in the ISGF3-IRF7 cascade, whose effect is bi-directional in a strain- and microbiota-dependent manner.

【 授权许可】

Unknown   
© Munakata et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.