| Project/Area Number |
22590145
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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 |
Medical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 細菌由来スーパー抗原 / ヒト末梢リンパ球 / 制御性 T 細胞 / 抗菌薬 / 脂溶性ビタミン / ヒ素化合物 / 免疫抑制薬耐性 / T細胞マイトゲン / 制御性T細胞 / ビタミンK誘導体 / 抗癌薬 / CD4陽性細胞 / CD25陽性細胞 / 末梢血単核細胞(PBMC) / 制御性T細胞(T reg) / MAPK / マクロライド系抗生物質 / 亜ヒ酸 / ビタミンK / 抗微生物薬 / サイトカイン / 亜ヒ酸(As203) |
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| Research Abstract |
It has been suggested by our previous studies that superantigen-stimulated human peripheral-blood mononuclear cells (PBMCs) show continuous IL-2 producing ability, possibly via elevation of mitogen-activated protein kinase (MAPK) activity. However, it has still been unclear about relationship between these abnormal activations and the regulatory T (Treg) cell frequencies in PBMCs stimulted by bacterial superantigen or T cell mitogen. Such information would be useful for providing new strategies for overcoming clinical resistance to immunosuppressive therapy often observed in patients with autoimmune diseases. Then, we examined frequency of Treg in the superantigen-stimulated PBMCs, and the effects of several antibiotics, As_2O_3, anticancer agents, and lipophilic vitamins. We showed that As_2O_3and anticancer agents increase the frequency of Treg cells in the activated PBMCs, whereas roxithromycin inhibits PBMC proliferation without influence on Treg cells, via inhibition of JNK activity. Among the lipophilic vitamins examined, vitamin K3 and K5inhibited the PBMC proliferation via increase in Treg frequency in the activated PBMCs. We alsofound that there would be correlations between Treg frequencies and the sensitivities to immunosuppressive drugs in PBMCs of SLE patients. Thus, we concluded that PBMCs stimulated with bacterial superantigen or T cell mitogen have decreased Treg frequencies,and As_2O_3, vitamin K_3 and K5inhibit PBMC proliferation via promotion of Treg frequency in the activated PBMCs
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