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

<p>Abstract</p> <p>Background</p> <p>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 bee...

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Main Authors: Munakata Kaori, Takashima Kiyoe, Nishiyama Mitsue, Asano Naoko, Mase Akihito, Hioki Kyoji, Ohnishi Yasuyuki, Yamamoto Masahiro, Watanabe Kenji
Format: Article
Language:English
Published: BMC 2012-01-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/13/30
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author Munakata Kaori
Takashima Kiyoe
Nishiyama Mitsue
Asano Naoko
Mase Akihito
Hioki Kyoji
Ohnishi Yasuyuki
Yamamoto Masahiro
Watanabe Kenji
author_facet Munakata Kaori
Takashima Kiyoe
Nishiyama Mitsue
Asano Naoko
Mase Akihito
Hioki Kyoji
Ohnishi Yasuyuki
Yamamoto Masahiro
Watanabe Kenji
author_sort Munakata Kaori
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>
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spelling doaj.art-afb0a411f56c433d826c83f91f9347672022-12-21T19:59:59ZengBMCBMC Genomics1471-21642012-01-011313010.1186/1471-2164-13-30Microarray 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 cascadeMunakata KaoriTakashima KiyoeNishiyama MitsueAsano NaokoMase AkihitoHioki KyojiOhnishi YasuyukiYamamoto MasahiroWatanabe Kenji<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2164/13/30
spellingShingle 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
BMC Genomics
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://www.biomedcentral.com/1471-2164/13/30
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