Analysis of regulatory mechanisms for HMGB1 secretion and signal transduction and their clinical significance
| Project/Area Number |
16390517
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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 |
Emergency medicine
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
OZAKI Shoichi St.Marianna Univ Sch Med, Professor, 医学部, 教授 (00231233)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Toshihiro St.Marianna Univ Sch Med, Professor, 難病治療研究センター, 教授 (90260752)
TAIRA Yasuhiko St.Marianna Univ Sch Med, assistant Professor, 医学部, 助教授 (00154724)
YOSHIDA Michiteru Science Univ of Tokyo, Professor (20005648)
KOIKE Kaoru Tohoku Univ., assistant Professor (10267164)
井田 伸夫 東レ株式会社, 先端融合研究所, 主任研究員
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2004: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | HMGB1 / HMGB1 receptors / Signal transduction / B-cell epitopes / cytotoxic T cells / T-cell epitopes / Hepatic-failure models / HMGB1-absorption therapy / マクロファージ / エピトープ / 好中球 |
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| Research Abstract |
We isolated high mobility group (HMG) nonhisitone chromosomal proteins 1 and 2 (HMGB1/HMGB2) as target antigens of anti-neutrophil cytoplasmic antibody, and have been analyzing the roles of those autoantibodies as well as the autoantigens.
In this study, we found that the major B-cell epitope of a monoclonal anti-HMGB1 antibody, FBH7, is a combinatorial structure which is constructed by amino acid residue 52-56, ant that this portion is different between neutrophil-derived and lymphocyte-derived HMGB1 (J.Biochem.136;155,2004). We also analyzed the HMGB1 epitopes that were recognized by serum antibodies derived from patients with various autoimmune diseases : rheumatic diseases, inflammatory bowel diseases, and autoimmune liver diseases. Although we have not completed the epitope mapping, data obtained so far indicate that some sera recognize the similar epitope.
The T-cell epitope of HMGB1 was investigated by measuring the affinity to bind to HLA-A2.1. We revealed that the 9-mer of HMGB1 12-20 showed the similar affinity as a well-known CTL epitope, p17-WT. These results suggest that HMGB1 may induce CTL restricted to HLA-A2.1.
We also established a novel fatal mouse model, in which 90% of the hepatic blood flow was blocked by a surgical procedure. All mice died 60 hr after the ligation with a median survival time of 30 hr. These mice showed an elevated level of serum HMG1, and the survival rate increased by a simultaneous i.p.injection of monoclonal anti-HMG1 antibody (J.Surg.Res.124:59,2005). Taken together, these data indicates that HMG1 protein may play an important role in a certain fatal condition, and that the intervention of serum HMG1 levels may serve as a new strategy for such a critical state. For that purpose, we started to establish a biological membrane that can absorb HMGB1 effectively.
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Report
(3 results)
Research Products
(30 results)
