| Project/Area Number |
10357007
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pediatrics
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| Research Institution | Fukui Medical University |
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Principal Investigator |
MAYUMI Mitsufumi Fukui Medical Univ.Dept.of Pediatrics, Professor, 医学部, 教授 (70135581)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Yushi Oriental Yeast Co.Nagahama Research Institute, Director, バイオ部, 取締役(研究職)
YODOI Junji Kyoto Univ.Institute for Virus Research, Professor, ウイルス研究所, 教授 (80108993)
KATAMURA Kenji Kyoto Univ.Graduate School of Medicine, Dept.of Pediatrics, Lecturer, 医学研究科, 講師 (40185806)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥24,900,000 (Direct Cost: ¥24,900,000)
Fiscal Year 2000: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1999: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥11,200,000 (Direct Cost: ¥11,200,000)
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| Keywords | food allergy / egg allergy / hypoallergic food / ADF / thioredoxin / tolerance / regulation / レドックス制御 |
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| Research Abstract |
In order to provide eatable eggs for egg allergy patients and a therapeutic tool for tolerance induction in them, we examined whether or not ADF/Thioredoxin(TRX)could reduce the antigenic activity of ovalbumin(OVA)and ovomucoid(OM), two major antigens of eggs which is the most common food allergen in childhood. TRX can successfully reduce the intramolecular disulfide bonds in OVA and OVM, and make them susceptible to the treatment with digestive enzymes such as pepsin and trypsin and heat. OVA and OM treated with TRX and the digestive enzymes or heat showed a hundred times decrease in the binding activity to specific IgE antibodies, showing that TRX is useful to make hypoallergic egg allergens.
To examine whether or not the TRX-treated hypoallergic eggs are useful for early intervention of food allergy through induction of oral tolerance, we established a mouse model in which eczema and OVA specific IgE were induced by skin sensitization with OVA.We found that oral administration of OVA to the mouse induced an oral tolerance ; a decrease in anti-OVA IgE level and antigen-specific IL-4 and IFN-γ secretion. We are going to examine the effect of the hypoallergic OVA on the induction of oral tolerance by using the mouse model.
We also found the followings ; TRX plays a role in signal transduction for apoptosis through maintaining the caspase 3 activity, TRX activates transcriprional factor p53 in combination with Ref-1, TRX inhibits the extravasation of granulocytes, geranylgeranylacetone enhances expression and secretion of TRX, and Thioredoxin-binding protein 2/Vitamin D3-upregulated protein-1(TBP-2/VDUP-1)is an inhibitor of TRX.All these data provide the basis for application of TRX for the treatment of allergic diseases.
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