| Project/Area Number |
10670442
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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 | ASAHIKAWA MEDICAL COLLEGE |
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Principal Investigator |
NAKAMURA Kimihide ASAHIKAWA MEDICAL COLLEGE, MEDICINE II, ASSOCISTE PROFESSOR., 医学部, 助教授 (20217839)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Concanavalin A / Liver injury model / Cytokine / Chemokine / Autoimmune hepatitis / Hyaluronic acid (HA) / Antithrombin III (AT-III) / Macrophage inflammatory protein-2 (MIP-2) / 免疫学的肝細胞障害 / Macrophage inflammatory protein-2 / 白血球 / Tリンパ球 / サイトカン / 性差 / ウルソデオキシコール酸 |
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| Research Abstract |
(1) Concanavalin A (Con A) induces T-cell dependent hepatic injury in mice. Among various cytokines produced by activated T-cells, tumor necrosis factor α(TNF-α) and interferon gamma (IFN-γ) are considered to play critical roles in this model. In this study, Con A induces more severe liver injury in female mice than male mice and the overexpression of serum proinflammatory cytokines (TNFα, and IFN-γ) was considered to be gender-associated differences. This model allow the investigation of the pathogenesis of immunological liver injury as well as pharmacological studies for the development of hepatoprotective drugs.
(2) Macrophage inflammatory protein-2 (MIP-2), one of CXC chemokines, induced by TNF-α is involved in the recruitment of neutrophils. I investigated a role of MIP-2 in Con A-induced liver injury in mice. This study revealed that plasma MIP-2 was induced by INF-α produced after Con A administration and contributes to the liver injury in Con A-induced liver injury.
(3) I investigated whether an exogenous administration of antithrombin III (AT-III) and hyaluronic acid (HA) influences the Con A-induced liver injury and cytokine production. This study revealed that AT-III prevented the liver injury by reducing MIP-2 production and high molecular but not low molecular weight HA prevented the liver injury by reducing proinflammatory cytokines (INF-α and IFN-γ) production in Con A-induced liver injury model.
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