| Project/Area Number |
16590625
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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 |
Gastroenterology
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
KOBAYASHI Eiji (2005) JICHI MEDICAL SCHOOL, School of Medicine, Professor, 医学部, 教授 (00245044)
金子 隆志 (2004) 自治医科大学, 医学部, 助手 (10254913)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Takashi JICHI MEDICAL SCHOOL, School of Medicine, Assistant Professor, 医学部, 講師 (00326852)
HAKAMATA Yoji JICHI MEDICAL SCHOOL, School of Medicine, Assistant Professor, 医学部, 講師 (00218380)
小林 英司 自治医科大学, 医学部, 教授 (00245044)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Chronic hepatitis / Viral hepatitis / Lymphocyte homing / FTY720 / KRP-203 / ウイルス性肝炎 |
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| Research Abstract |
T cell-mediated immune responses play a critical role in a variety of liver injuries including autoimmune hepatitis. Injection of concanavalin A (Con A) into mice mimics the histological and pathological phenotype of T cell-mediated hepatitis. Recent advances in host immune control of organ transplantation include the development of sphingosine-1-phosphate (S1P) receptor agonists such as FTY720, which alter lymphocyte homing but do not suppress host general immunity. Herein we examined the effect of the new S1P receptor agonist KRP-203 on the Con A-induced liver damage model. In normal liver lymphocytes of BALB/c mice, both FTY720 and KRP203 promoted lymphocyte sequestering from the liver to secondary lymph nodes and significantly reduced the number of liver lymphocytes (p<0.05). Based on this observation, KRP203 was employed in the Con A-induced hepatitis model. KRP203 markedly reduced the number of CD4^+ lymphocytes that infiltrate Con A-treated liver (p<0.05) and successfully reduced serum transaminase elevation (p=0.017), therefore protecting mice from Con A-induced liver injury. Interestingly this homing modulation less occur in natural hepatic T cell homing through the chemokine receptor, CXCR4. Therefore, S1P receptor agonists preferentially target CXCR4^+CD4^+ peripheral blood T lymphocytes and suppress the occurrence of Con A-induced hepatitis, suggesting their therapeutic usefulness against T cell-mediated hepatic injury.
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