| Project/Area Number |
12672176
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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 |
Environmental pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
OHSAWA Motoyasu Teikyo University, Faculty of pharmaceut. Sci. Professor., 薬学部, 教授 (30129978)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kazuko Teikyo University, Faculty of pharmaceut. Res. Assoc., 薬学部, 助手 (90163245)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | oral immune tolerance / ovalbumin / mouse / phenanthrene / antibody production cytokine / サイトカイン / エストラジオール / シクロホスファミド |
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| Research Abstract |
Immune tolerance is a defense mechanism against induction of hyperimmune response like oral allergy, and the tolerance can be impaired by environmental chemicals. This research was undertaken to study a mechanism for chemical-induction of undesired antibody production through impairment of oral immune tolerance. For the purpose, the study was planed first to establish an oral tolerance model of mice, second to examine if the tolerance can be modified by some chemicals such as cyclqphosphamide (CP), estradiol (E2) and phenanthrene (PT), and to analyze mechanisms of their modification of the tolerance. Results were as follows :
1. A mouse model of oral tolerance was established by use of ovalbumin (OVA) as an antigen. Female BALB/c mice given an oral administration of OVA resulted in stable tolerance of antibody production against OVA, that was effective to both Th1 and Th2 cell functions.
2. In this model, chemicals such as CP, E2 and PT at high dose and given with oral OVA promoted production of antibodies against OVA and turned the tolerance less effective. The modification of the tolerance was characterized by preferable induction of IgG1 and further suppression of IgG2a against OVA, meaning dominant Th2 function.
3. PT that promoted production of anti-OVA IgG1 dose-dependently preferably inhibit production of IFN-y rather than that of IL-4 in spleen cell cultures. Cultured spleen cells from the model mice of the tolerance given PT also gave less production of IFN-y compared with IL-4.
These findings indicate that PT promoted excess production of antibodies via Th2 cell activation by modification of oral immune tolerance. It is also suggested that chemical-induction of hyperimmune response including allergy can be caused by such mechanism.
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