2000 Fiscal Year Final Research Report Summary
NUCLEOLIN AS THE EARLIEST TARGET MOLECULE OF AUTOANTIBODIES PRODUCED IN MRL/lpr LUPUS PRONE MICE
| Project/Area Number |
11670454
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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 |
MINOTA Seiji JICHI MEDICAL SCHOOL, DEPARTMENT OF MEDICINE, PROFESSOR, 医学部, 教授 (30211593)
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| Project Period (FY) |
1999 – 2000
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| Keywords | systemic lupus erythematosus / autoantibody / MRL / lpr mouse / NZB / NZW F1 mouse / anti-DNA antibody / anti-nucleolin antibody |
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| Research Abstract |
To elucidate the autoantigen against which autoantibodies are produced in the earliest phase of the disease process of systemic lupus erythematosus (SLE), serum samples were collected individually and serially from 10 NZB/NZW F1 and 10 MRL/lpr mice. Using immunoblots with mouse thymoma cell (EL-4) lysates as substrates, all mice were found to generate autoantibody against either 150kDa. 110kDa, 75kDa or 55kDa molecule as early as 4 weeks. Anti-DNA antibodies occurred almost at the same time or after those against these four molecules. The number of antigens reactive with autoantibodies in immunoblots increased gradually with age. Antibodies against histone molecules were produced after 8 weeks of age. Among the four antigens, the 110kDa molecule was identified as nucleolin, which is an abundant nucleolar phosphoprotein. Nucleolin binds DNA, RNA and nucleic-acid binding proteins such as histone H1. Nucleolin is a target of granzyme A of cytotoxic T cells, and autoantibodies against it are found in sera from patients with SLE as well as those with various viral infections. These results indicate that nucleolin is one of the immunodominant molecules which break down self-tolerance and initiate autoantibody-spreading in mouse model of SLE.
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[Publications] Hirata,D.,Iwamoto,M.,Yoshio,T.,Okazaki,H.,Masuyama,J.,Mimori,A.and Minota,S.: "Nucleolin as the earliest target molecule of autoantibodies produced in MRL/lpr lupus-prone mice."Clin.Immunol.. 97(1). 50-58 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Mimori,A.,Suzuki,T.,Nakajima,K.,Masuyama,J.,Yoshio,T.,Kano,S.and Minota,S.: "Clinical features of dermatomyositis in the presence or absence of malignancy."APLAR J.Rheumatol.. 3(3). 217-220 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Mimori,A.,Suzuki,T.,Satoh,N.,Nara,H.,Masuyama,J.,Yoshio,T.,Kano,S.and Minota,S.: "Dermatomyositis and cutaneous necrosis : report of five cases."Mod.Rheumatol.. 10. 117-120 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Okazaki,H.,Sato,H.,Kamimura,T.,Hirata,D.,Iwamoto,M.,Yoshio,T.,Mimori,A.,Masuyama,J.,Kano,S.and Minota,S.: "In vitro and in vivo inhibition of activaaation induced T cell apoptosis by bucillamine."J.Rheumatol.. 27. 1358-1364 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Mimori,A.,Suzuki,T.,Hashimoto,M.,Nara,H.,Yoshio,T.,Masuyama,J.,Okazaki,H.,Hirata,D.,Kano,S.and Minota,S.: "Subarachnoid hemorrhage and systemic lupus erythematosus."Lupus. 9. 521-526 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Hirata, D., Iwamoto, M., Yoshio, T., Okazaki, H., Masuyama, J., Mimori, A.and Minota, S.: "Nucleolin as the earliest target molecule of autoantibodies produced in MRL/lpr lupus-prone mice."Clin.Immunol.. 97(1). 50-58 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Mimori, A., Suzuki, T., Nakajima, K., Masuyama, J., Yoshio, T., Kano, S.and Minota, S.: "Clinical features of dermatomyositis in the presence or absence of malignancy."APLAR J.Rheumatol.. 3(3). 217-220 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Mimori, A., Suzuki, T., Satoh, N., Nara, H., Masuyama, J., Yoshio, T., Kano, S.and Minota, S.: "Dermatomyositis and cutaneous necrosis : report of five cases."Mod Rheumatol.. 10. 117-120 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okazaki, H., Sato, H., Kamimura, T., Hirata, D., Iwamoto, M., Yoshio, T., Mimori, A., Masuyama, J., Kano, S.and Minota, S.: "Invitro and invivo inhibition of activation induced T cell apoptosis by bucillamine."J.Rheumatol.. 27. 1358-1364 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shimpo, M., Ikeda, U., Maeda, Y., Ueno, S., Ikeda, M., Minota, S., Takizawa, T., Urabe, M., Kume, A., Monahan, J., Ozawa, K.Shimada, K.: "Gene transfer into rat renal cells using adeno-associated virus vectors."Am.J.Nephrol.. 20. 242-247 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yokota, S., Hirata, D., Minota, S., Higashiyama, T., Kurimoto, M., Yanagi, H., Yura, T.and Kubota, H.: "Autoantibodiees against chaperonin CCT in human sera with rheumatic autoimmune diseases : comparison with antibodies against orher Hsp60 family proteins."Cell Street & Chaperones.. 5(4). 337-346 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Mimori, A., Suzuki, T., Hashimoto, M., Nara, H., Yoshio, T., Masuyama, J., Okazaki, H., Hirata, D., Kano, S.and Minota, S.: "Subarachnoid hemorrhage and systemic lupus erythematosus."Lupus.. 9. 521-526 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ikeda, U., Shinpo, M., Ohki, R., Takahashi, M., Yamamoto, K., Ikeda, M., Minota, S.and Shimada, K.: "Amlodipine increases nitric oxide synthesis in cytokine-stimulated cultured vascular smooth muscle cells."J.Hypertension.. 18(11). 1597-1604 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Chen, H., Ikeda, U., Shinpo, M., Ikeda, M., Minota, S.and Shimada, K.: "Fluvastain upregulates inducible nitric oxide synthase expression in cytokine-stimulated vascular smooth muscle cells."Hypertension.. 36. 923-928 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Iwamoto, M., Ogawa-Shirota, Y., Sato, H., Yoshio, T., Okazaki, H., Fujita, A., Sugimoto, H.and Minota, S.: "Early diagnosis of Takayasu arteritis using gadolinium-contrasted MRI."Arthritis Rheum.. 42. 1549 (1999)
Description
「研究成果報告書概要(欧文)」より
