| Project/Area Number |
20390203
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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 |
Gastroenterology
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
KIMURA Kiminori Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 研究員 (70397339)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIMI Kazuhiro 東京大学, 医学部附属病院, 特任准教授 (80273358)
NAGAKI Masahito 岐阜大学, 医学部附属病院, 臨床教授 (30293559)
SAIO Masanao 岐阜大学, 医学系研究科, 准教授 (40242721)
KURACHI Makoto 東京大学, 医学系研究科, 助教 (00396722)
UEHA Satoshi 東京大学, 医学系研究科, 特任助教 (00447385)
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUSHIMA Kouji 東京大学, 医学系研究科, 教授 (50222427)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 肝臓学 / 免疫 / B型肝炎ウイルス / CTL / ケモカイン / 肝障害 / 接着因子 / CD44 |
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| Research Abstract |
There are many uncertain points for regarding with leukocytes movement in the liver, especially interaction between liver sinus endothelial cells (LSECs) and cytotoxic T lymphocytes (CTLs). We examined role of CD44 for these interaction using hepatitis model. CTLs were administered into Hepatitis B virus transgenic mice (HBVTg) mice and HBVTgxCD44 knock out (KO) mice, and alanine aminotransferase activity, number of intrahepatic leukocytes, cytokine and chemokine mRNA level were examined. To determine the number and distribution of CTLs in the liver CFSE-labeled CTLs was administered into HBVTg with or without CD44 mice. sALT activity increased since 12 h though it had declined to 4 h in the CD44KOxHBVTg mice after CTLs injection. Similarly, the levels of Tumor necrosis factor (TNF) a, Interferon (IFN) g, Macrophage inflammatory protein (MIP)-2 mRNAs reduced in 4 h though it had been increased since 12 h in the CD44KOxHBVTg mice. The number of apoptotic hepatocytes increased intentionally at 24 h in the CD44KOxHBVTg livers, and it thought to be due to lower activity of initial nuclear factor kappaB (NF-kB). Although the number of CTLs exhibited lower at 4 h in the CD44KOxHBVTg livers the difference of Intercellular adhesion molecule (ICAM)-1 and CD86 expression on LSECs was not detected. CD44 on LSECs exerts important roles for CTLs migration into the hepatocytes. However, since CD44 deficient state was exacerbate hepatic injury, attention is necessary for hepatitis treatment as CD44 target therapy.
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