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

Kaori Munakata, Kiyoe Takashima, Mitsue Nishiyama, Naoko Asano, Akihito Mase, Kyoji Hioki, Yasuyuki Ohnishi, Masahiro Yamamoto, Kenji Watanabe

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: The 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.Results: In 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.Conclusions: Microarray 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.

Original languageEnglish
Article number30
JournalBMC Genomics
Volume13
Issue number1
DOIs
Publication statusPublished - 2012 Jan 18

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Traditional Medicine
Microarray Analysis
Interferons
Specific Pathogen-Free Organisms
Interferon Type I
Genes
Interferon Regulatory Factors
Interferon Inducers
Herbal Medicine
Microbiota
Large Intestine
Transcriptome
Small Intestine
Japan
Up-Regulation
Down-Regulation
juzentaihoto
Neoplasm Metastasis
Gene Expression
Therapeutics

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

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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. / Munakata, Kaori; Takashima, Kiyoe; Nishiyama, Mitsue; Asano, Naoko; Mase, Akihito; Hioki, Kyoji; Ohnishi, Yasuyuki; Yamamoto, Masahiro; Watanabe, Kenji.

In: BMC Genomics, Vol. 13, No. 1, 30, 18.01.2012.

Research output: Contribution to journalArticle

Munakata, Kaori ; Takashima, Kiyoe ; Nishiyama, Mitsue ; Asano, Naoko ; Mase, Akihito ; Hioki, Kyoji ; Ohnishi, Yasuyuki ; Yamamoto, Masahiro ; Watanabe, Kenji. / 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. In: BMC Genomics. 2012 ; Vol. 13, No. 1.
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abstract = "Background: The 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.Results: In 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.Conclusions: Microarray 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.",
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T2 - Acceleration of IFN-α response via affecting the ISGF3-IRF7 signaling cascade

AU - Munakata, Kaori

AU - Takashima, Kiyoe

AU - Nishiyama, Mitsue

AU - Asano, Naoko

AU - Mase, Akihito

AU - Hioki, Kyoji

AU - Ohnishi, Yasuyuki

AU - Yamamoto, Masahiro

AU - Watanabe, Kenji

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AB - Background: The 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.Results: In 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.Conclusions: Microarray 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.

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