| Project/Area Number |
17607004
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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 |
アレルギー
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| Research Institution | University of Yamanashi |
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Principal Investigator |
NAKAO Atsuhito University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院医学工学総合研究部, 教授 (80317445)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Allergy / TGF-p / Oral tolerance / Oral feeding / 食物アレルギー / サイトカイン / 治療法 |
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| Research Abstract |
Background: Epidemiological studies suggest that transforming growth factor-β (TGF-β) in breast milk provides protection against allergic disease during infancy. However, it is unclear whether orally administered TGF-β, such as TGF-β in human milk, retains and exerts its activity in the intestinal mucosa and can affect immune response (tolerance) to dietary antigens.
Objective: To determine whether orally administered TGF-β is biologically active in intestinal mucosa and affects oral tolerance.
Methods: Activity of orally administered TGF-β in the intestinal mucosa was evaluated by in vivo imaging using transgenic mice expressing a Smad-responsive reporter construct (SBE-luc mice), by immunohistochemical staining with anti-phosphorylated Smad2 antibody, and by real-time RT-PCR analysis of TGF-β and Smad7 mRNA expression. The effects of orally administered TGF-β on oral tolerance induction were assessed in mice tolerized by high-dose ovalbumin (OVA) feeding.
Results: The oral administration of TGF-β increased Smad-responsive reporter activity in the intestine of SBE-luc mice and induced Smad2 phosphorylation and TGF-β and Smad7 mRNA expression in the intestine of BALB/c mice. Serum TGF-6 levels were also increased after oral administration of TGF-β. BALB/c mice treated orally with OVA and TGF-I3 showed augmented reduction of OVA-specific IgE and IgG1 antibodies, T cell reactivity, and immediate-type skin reaction when compared with the mice treated orally with OVA alone.
Conclusions: Orally administered TGF-β retains sufficient biological activity in intestinal mucosa and enhances oral tolerance.
Clinical implications: Oral administration of TGF-β might become a potential strategy to prevent allergic disease such as food allergy.
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