1999 Fiscal Year Final Research Report Summary
HMG proteins : their intra-cellular trafficking and the role in inflammatory diseases
| Project/Area Number |
10470125
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
OZAKI Shoichi Kyoto Univ., Grad. Sch. Med, Lecturer, 医学研究科, 講師 (00231233)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Michiteru Science Univ Tokyo, Professor, 基礎工学部, 教授 (20005648)
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| Project Period (FY) |
1998 – 1999
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| Keywords | HMG proteins / HMG1 / HMG2 / anti-HMG antibody / autoimmune disease / Autoimmune hepatitis / epitopes / intra-cellular localization |
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| Research Abstract |
We found the existence of anti-HMG1/HMG2 antibodies in 89% of patients with autoimmune hepatitis. These antibodies seemed to be useful clinical markers in the disease based on the highest prevalence and the correlation with disease activity.
To determine the B-cell epitopes recognized by circulating autoantibodies, we performed western blotting, in which antigens were a set of recombinant fragment peptides of HMG1 and HMG2. Antibody-positive sera from patients with autoimmune hepatitis were used. Our results indicated that the epitopes are located within a linker region between the two HMG boxes.
We also investigated the mechanism of the selective staining of neutrophil by anti-HMG1/HMG2 antibodies. Affinity-purified anti-HMG1/HMG2 antibodies from patient serum reacted only with neutrophils, but not with lymphocytes, HEp-2 or HL60 cells(a promyelocytic leukemia cell line) in indirect immunofluorescence. After HL60 were treated with all-trans retinoic acid to induce granulocyte differentiation, however, these cells became reactive to the antibodies. In western blotting, the antibodies showed a distinct pattern of bands in neutrophils and differentiated HL60 cells, which was different from those in lymphocytes and untreated HL60 cells. Northern blotting revealed no significant difference in mRNA of HMG1 and HMG2 during differentiation of HL60 cells. These results indicated that the epitopes of HMG1/HGM2 molecules in neutrophils are disclosed or modified to become reactive to the antibodies during granulocyte differentiation.
The linker region, which we determined to be the major epitope, is known to be necessary for the nuclear localization of HMG proteins. It seems therefore that the change of antigenicity of the region may affect the nuclear localization signal and the efficiency of transcription in mature neutrophils.
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[Publications] Sobajima J., Ozaki S., Uesugi H., Osakada F., Inoue M., Fukuda Y., Shirakawa H., Yoshida M., Rokuhara A., Imai H., Kiyosawa K., Nakao K.: "High mobility group non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis."Gut. 44 (6). 3107-3314 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ochiai K. *, Ozaki S. *, Tanino A., Watanabe S., Ueno T., Mitsui K., Toei J., Inada Y., Hirose S., Shirai T., Nishimura H. (* the first two authors contributed equally to this work): "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice."Int. Immunol.. 12 (1). 1-8 (2000)
Description
「研究成果報告書概要(欧文)」より
