| Project/Area Number |
16591089
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YOKOZEKI Hiroo Tokyo Medical and Dental University, Dermatology, Professor, 大学院医歯学総合研究科, 教授 (90210608)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Takahiro Tokyo Medical and Dental University, Dermatology, Associate Professor, 大学院医歯学総合研究科, 助教授 (30235361)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Atopic dermatitis / third phase reaction / Gene therapy / STAT6 / Th2 cytokine / Eeosinophil / Mast cell / BAS / Th2 cytokine / おとり型核酸医薬 / 核酸医薬療法 / 遺伝子治療 / IgE / 遅発型反応 |
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| Research Abstract |
Professor Karasuyama has recently established transgenic mice that carry the genes cording for heavy and light chain of TNP-IgE as an atopic dermatitis (AD) mouse model. We therefore hypothesized that synthetic double-stranded DNA with a high affinity for STAT6 could be introduced in vivo as a decoy cis elements to bind the transcriptional factor and to block the gene activation of contributing the onset and progression of AD, thus providing effective therapy for AD. Treatment by the transfection of STAT6 decoy oligodeoxynucleotides (ODN), but not scrambled decoy ODN in the TNP-IgE transgenic mice, had a significantly inhibitory effect on not only STAT6 binding to nuclei but also on the third phase response (62% inhibition). A histological analysis revealed that both edema and the infiltration of eosinophils and degranulated mast cells significantly decreased in STAT6 decoy ODN transfected mice. We reported the successful in vivo transfer of STAT6 decoy ODN to reduce the third phase reaction in TNP-IgE transgenic mice, thereby providing a new therapeutic strategy for atopic dermatitis.
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