1999 Fiscal Year Final Research Report Summary
The immunosuppressive function of the α-fetoprotein
| Project/Area Number |
10670131
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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 |
Pathological medical chemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NISHI Shinzo Hokkaido Univ., Sch. Med., Pro., 医学部, 教授 (20001894)
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| Co-Investigator(Kenkyū-buntansha) |
NAKABYASHI Hidekazu Hokkaido Univ., Grad. Sch. Med., Inst., 医学部, 助手 (10033383)
SAKAI Masaharu Hokkaido Univ., Sch. Med., Asso. Pro., 医学部, 助教授 (50162269)
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| Project Period (FY) |
1998 – 1999
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| Keywords | α-fetoprotein / immunosuperssion / auto-imune doseases / T-cell / hepatocellular cacinoma / transgenic mice |
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| Research Abstract |
α-fetoprotein (AFP) is a serum protein in appreciable amounts in fetal but not in adult serum. However, serum AFP is frequently elevated in patients with hepatocellular carcinomas and yolk sac tumors. Numerous studies have suggested that immunomodulation may be one of the biological functions of AFP. To clarify the biological function of the AFP in vivo, we have established a transgenic mouse, which has a human AFP gene under the control of β-actin promoter. In this mouse, ubiquitous expression of AFP is observed. Using these mice, we have been analyzed experimental autoimmune diseases, such as arthritis, autoimmune thyroiditis and experimental encephalomyelitis. We have showed that development of all these experimental autoimmune diseases were significantly suppressed in AFP produced transgenic mice compared with wild mice. In vitro phytohemagglutinin response of splenocytes from transgenic mice was lower than that from wild mice. Significantly reduced numbers of CD4+, CD8+ thymocytes were found in the transgenic mice. These observations suggest that ubiquitously produced AFP modulate in vivo T cell development and/or T cell dependent immune responses. Now, we have constructed the targeting plasmid for establishment of the AFP gene disrupted mice.
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Research Products
(12 results)
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[Publications] Nishihira, J., Fujunaga, M., Kuriyama, T., Suzuki, M., Sugimoto. H., Nakagawa, A., Tanaka, I., and Sakai, M.: "Molecular cloning of human D-Iopachrome tautomerase CDNA : N-Terminal proline is essential for enzyme activation"Biochem. Biophys. Res. Commun.. 243. 538-544 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Hirokawa, J., Sakaue, S.. Furuya, Y., Ishii, J., Hasegawa, A., Tagami, S., Kawakami, Y., Sakai, M., Nishi, S. and Nishihira, J.: "Tumor necrosis factor-alpha regulates the gene expression of macrophage migration inhibitory factor through tyrosine kinase-dependent pathway in 3T3-L1 adipocytes."J. Biochem.. 123. 733-739 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsuura, E., Kang, Y., Kitakawa, H., Ogata, A., Kotani, T., Ohtaki, S., Nishi, S.: "Modulation of T cell function by alpha-fetoprotein : An in vivo study on porcine thyroid peroxidase-induced experimental autoimmune thyroiditis in transgenic mice producing human alpha-fetoprotein"Tomor Biology. 20. 162-171 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamamoto R., Wakui Y., Taketa, K., Ishikura H., Sakuragi, N., hattori R., Sato H., Ebina. Y., Nishi, S., Fujimoto, S.: "A study on the lectin reactivity of alpha-fetoprotein produced by hepatoid adenocarcinoma and yolk sac tumors."Tomor Biology. 20. 212-217 (1999)
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「研究成果報告書概要(欧文)」より
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