| Project/Area Number |
14570432
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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 | Yokohama City University School of Medicine |
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Principal Investigator |
MITSUHIRO Takeo Yokohama City University Graduate School of Medicine and School of Medicine, Departments of Internal Medicine and Clinical Immunology, Associate Professor, 医学部, 講師 (50236494)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Noboru St.Marianna University School of Medicine, Departments of Immunology and Medicine, Professor, 医学部, 教授 (40235982)
UEDA Atsuhisa okohama City University Graduate School of Medicine and School of Medicine, Departments of Internal Medicine and Clinical Immunology, Associate Professor, 医学部, 講師 (60295483)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Behcet's disease / toll like receptor / tumor necrosis factor / NK cell / heat shock protein / heme oxygenase-1 / 炎症性サイトカイン |
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| Research Abstract |
It has been discussed that microbial pathogens is implicated in the development of autoimmune diseases such as Behcet's disease. One of the putative pathogenic antigens is 65 kD of heat shock protein (HSP) which are conserved during evolution and has a potent immunostimulatory property, leaking to cross reaction between microbial and host HSP. In addition, HSP is one of the ligands against toll like receptor (TLR) 4. We investigated involvement immune system, especially TLR in patients with Behcet's disease.
We monitored cytokine profile by using ELISPOT techniques during anti-tumor necrosis factor(TNF)-alfa monoclonal antibody therapy or Behcet's disease patients with refractory uveitis. The results revealed that anti-TNF-alfa mAb therapy significantly reduced circulating TNF-alfa producing cells, which was closely associated with clinical remission (Misumi M, Takeno M, et al. Cytokine 24(5):210, 2003) Next, we found abnormal expression of killer inhibitory receptor in NK cells from the patients (Takeno M, et al. Rheumatol Int, (in press)). These findings indicated that innate immune system is impaired in the disease.
We examined mRNA expression of TLR 2,4, and 9 in peripheral mononuclear cells and pleomorphic nuclear cells by real time PCR technique, but did not find any abnormalities in patients with Behcet's disease. We next studied expression of heme oxygenase-1, which has anti-inflammatory properties and increased in patients with adult still's disease. The data showed that high levels of HO-1 protein and mRNA were expressed in pleomorphic nuclear cells (neutrophils) from patients with Behcet's disease when compared with normal controls. The data suggest that the regulatory system of inflammation is impaired in the disease.
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