POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
THURSDAY, 5:30-6:15 PM
Munakata K, Miura N, Yamamoto M, Ishige A, Watanabe
K.
Transcriptome analysis of the effect of a herbal medicine
Juzentaihoto—Implications for mechanism of prevention of infection.
Kampo medicine, Keio University School of Medicine
di055014@sc.itc.keio.ac.jp
INTRODUCTION: Recently, a lot of fatal infectious
diseases have now become treatable by development of the antibiotics.
However, a prevalence of the drug resistant pathogens and the emergence
of new infectious diseases such as avian influenza and severe acute
response syndrome (SARS) are increasing serious threats to global public
health. Therefore it is no doubt about the necessity of new therapeutic
strategies, which combats new (or often unknown) viruses and drug-resistant
microorganisms by potentiating the innate host defense systems which
respond to a wide variety of microorganisms rapidly and in a relatively
nonspecific manner. Juzen-taiho-to (JTT), a hot water extract from a
mixture composed of 10 medicinal plants, is one of commonly used Kampo
(Chinese-Japanese traditional) medicines. In clinical research, JTT
has been investigated for the beneficial effects including antitumor
activity, prevention of infection and improvement of alimentation. Basic
research has demonstrated that JTT possesses certain biological activities
such as activation of immune systems, protection against infectious
diseases, antitumor activity, prevention of cancer metastasis, and alleviation
of the symptoms of fatigue. To identify the molecular pathway by which
JTT exerts preventive effect against various infectious diseases, we
used the Affymetrix GeneChip arrays to profile gene expression in the
large intestine which is supposed to be one of possible target tissues
of this drug.
METHOD: SPF male IQI mice (age 7 to 9 weeks)
were orally treated with JTT solution (0.1 g/ml/10g body weight) or
water daily for 14 days. Labeled cRNA prepared from total RNA of the
large intestine was hybridized to the GeneChip Murine Genome U74A V.2
(Affymetrix). RT-PCR was used to confirm the results of GeneChip analyses.
RESULT & DISCUSSION: GeneChip and RT-PCR analysis
revealed significant increase in expression of the interferon (IFN)
alpha-related genes such as IFN-stimulated gene factor 3 (ISGF3), IFN
regulatory factor 7 (IRF7), and IFN-induced protein with tetratricopeptide-repeats
1 (IFIT1) in JTT-treated mice. The gene induction of type 1 IFN is rapid,
and can be divided into two distinct phases. In the first phase, IFN
beta is synthesized. In the second phase, secreted IFN beta triggers
the autocrine pathways of massive IFN alpha production through IFN receptor.
Among IFN-related genes involved in this positive feedback loop, the
basal level of ISGF3 and IRF7 proteins has been known to correlate with
the magnitude of IFN alpha response. Because JTT gave no influence on
the expression of IFN beta and IFN alpha, the drug is not an IFN inducer.
However, the up-regulation of basal level of ISGF3 and IRF7 by JTT may
result in the rapid and enhanced IFN alpha production when invading
pathogens trigger the type 1 IFN signaling. It is thus suggested that
the preconditioning of signaling pathway to IFN alpha production by
JTT is involved in JTT's protective activity against various infectious
diseases.
Back