| Project/Area Number |
06454341
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAGATAKI Shigenobu Nagasaki University, School of Medicine, Professor, 医学部, 教授 (70010311)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Naokata Nagasaki University, School of Medicine, Assistnt, 医学部, 助手 (10240219)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1994: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Autoimmune thyroid diseas / Thyrotropin (TSH) receptor / TSH receptor antibody / Fusion protein / TSH受容体蛋白 / 融合蛋白(TSHR-MBP) / 巣状甲状腺炎 |
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| Research Abstract |
Both humonal and cellular immunity play an important role in the pathogenesis of autoimmune thyroid disease (AITD). It remains, however, to be elucidated whether the thyrotropin receptor (TSHR) protein is involved in pathogenesis of AITD through cellular immunity. In the present disease, we expressed the extracellular domain of TSHR as a fusion protein with maltose-binding protein (TSHR-MBP) in bacteria and examined its abilities to induce functionally relevant anti-TSHR antibodies and experimental autoimmune thyroiditis in four different H-2 strains of mice and also to interact with TSH and Graves'sera. TSHR-MBP fusion protein was expressed in a soluble form and purified with an amylose resin column and gel extraction. Immunization with purified TSHR-MBP as well as purified MBP fused to a short sequence of beta-galactosidase elicited a good serum antibody-response to these proteins, but not functionally relevant anti-TSHR antibodies or experimental thyroiditis, in all strains of mice examined. Nevertheless, the significant decrease in serum concentrations of thyroxine was observed in majority of mice immunized with either TSHR-MBP or MBP-beta gal, suggesting a non-specific effect of immunization. Finally, neither TSH or Graves' sera could bind to MBP-TSHR specifically. These data, although some are contradictory to previous reports, suggest that the TSHR extracellular domain may not play a significant role in cellular immunity for the pathogenesis of AITD at least in an animal model, and further reinforce our previous conclusion that TSH and anti-TSHR autoantibodies in patients with AITD interact with conformationally intact TSHR.
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