2005 Fiscal Year Final Research Report Summary
Development of the lymphocyte-homing modulator against hepatitis
| 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 JICHI MEDICAL SCHOOL, School of Medicine, Professor, 医学部, 教授 (00245044)
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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)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Chronic hepatitis / Viral hepatitis / Lymphocyte homing / FTY720 / KRP-203 |
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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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[Journal Article] Efficacy of mycophenolic acid combined with KRP-203, a novel immunomodulator, in a rat heart transplantation model.2006
Author(s)
Suzuki C, Takahashi M, Morimoto H, Izawa A, Ise H, Fujishiro J, Murakami T, Ishiyama J, Nakada A, Nakayama J, Shimada. K, Ikeda U, Kobayashi E.
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Journal Title
J Heart Lung Transplant. 25
Pages: 302-309
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts.2005
Author(s)
Shimizu H, Takahashi M, Kaneko T, Murakami T, Hakamata Y, Kudou S, Kishi T, Fukuchi K, Iwanami S, Kuriyama K, Yasue T, Enosawa S, Matsumoto K, Takeyoshi I, Morishita Y, Kobayashi E.
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Journal Title
Circulation 111
Pages: 222-229
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A novel immunomodulator KRP-203 combined with cyclosporine prolonged graft survival and abrogated transplant vasculopathy in rat heart allografts.2005
Author(s)
Takahashi M, Shimizu H, Murakami T, Enosawa S, Suzuki C, Takeno Y, Hakamata Y, Kudou S, Izawa S, Yasue T, Kobayashi E.
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Journal Title
Transplant Proc. 37
Pages: 143-145
Description
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