| Project/Area Number |
09670489
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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 |
内科学一般
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| Research Institution | Jichi Medical School |
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Principal Investigator |
KANO Shogo Jichi Medical School, Medicine, Professor, 医学部, 教授 (00049024)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIO Taku Jichi Medical School, Medicine, Ass.Professor, 医学部, 講師 (20221666)
MASUYAMA Jun-ichi Jichi Medical School, Medicine, Ass.Professor, 医学部, 講師 (20165731)
OKAZAKI Hitoaki Jichi Medical School, Medicine, Ass.Professor, 医学部, 講師 (40285789)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | systemic lupus erythematosus / apoptosis / ceramide / rheumatoid arthritis / transendothelial migration / anti-ribosomal P0 protein antibody / 抗リボゾームP0蛋白抗体 / 自己免疫 / 抗血管内皮細胞抗体 / 血管外遊走 / FTY720 |
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| Research Abstract |
1. MRL-lpr/lpr mouse has defect in apoptosis due to abnormal Fas gene and develops autoimmune diseases. Ceramide is an important mediator of intracellular signal transduction from Fas-Fas ligand interaction, and the cell membrane-permeable form C2-ceramide induced apoptosis in CD3+CD4-CD8-(DN) T cells from MIRL-lprllpr mice. FTY72O is a novel immunosuppressive agent resembling sphingosine in chemical structure. Oral administration of FTY72O as well as C2-ceramide reduced the number of DN T cells in lymph nodes and spleen of MRL-lpr/lpr mice, and significantly prolonged the survival at nine months.
2. A monoclonal antibody (4C8) was established, which inhibits the transendothelial migration of T cells without interfering their adhesion to endothelial cells. The 4C8 molecule also acts as the second signal of T cell activation.
3. Significantly elevated level of anti-endothelial cell antibody was found in SLE patients associated with pulmonary hypertension. One of the antigen recognized by anti-endothelial cell antibodies was identified as ribosomal P0 protein. Anti-ribosomal PG protein antibodies were found in sera from the patient with systemic lupus erythematosus(SLE). Positive anti-ribosomal P0 protein antibodies were associated with central nervous system involvement in SLE.A close temporal relationship of liver disease to anti-ribosomal P0 protein antibodies and central nervous system disease was also found in SLE patients.
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