Extracellular Branched-chain Amino Acids, Especially Valine, Regulate Maturation and Function of Monocyte-derived Dendritic Cells
| Project/Area Number |
17590609
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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 | TOHOKU UNIVERSITY |
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Principal Investigator |
UENO Yoshiyuki (2006) TOHOKU UNIVERSITY, HOSPITAL, LECTURER, 病院, 講師 (70282126)
菅野 記豊 (2005) 東北大学, 病院, 助手 (70375004)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Koji TOHOKU UNIVERSITY, HOSPITAL, Research associate, 病院・助手 (20400476)
KOGURE Takayuki TOHOKU UNIVERSITY, HOSPITAL, Senior Residents, 病院・医員 (70400330)
上野 義之 東北大学, 病院・講師 (70282126)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | dendritic cell / branched chain amino acid / natal immunity / liver failure / hapatocellular carcinoma / liver cirrhosis / 分岐鎖アミノ酸 |
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| Research Abstract |
The functions of dendritic cells (DCs) are impaired in patients with liver cirrhosis. It is well known that cirrhotic patients show decreased levels of plasma branched-chain amino acids (BCAA). Although amino acids are associated with maintaining the cell structure and function in many organs, limited data are available regarding the role of amino acids including BCAA in the immune system. We aimed to investigate the roles of BCAA in the function of human monocyte-derived DCs (MoDC). CD14-positive monocytes (CD 14 (+)) were isolated from PBMC from healthy volunteers and HCV cirrhotic patients. In medium deprived of BCAA or valine, monocytes were able to differentiate into immature DCs, but not into mature DCs, and showed their weak expression of CD83. The deprivation of leucine or isoleucine did not affect this process. The MoDC allo-stimulatory capacity was significantly decreased in medium deprived of BCAA or valine. Annexin V-FITC/PI staining showed the numbers of dead and apoptotic cells were not significantly different under any medium. Immunoblotting demonstrated that depletion of valine or leucine decreased P-S6 kinase expression. Valine increased dose-dependently the allo-stimulatory capacity and IL-12 production of MoDC from both healthy volunteers and HCV cirrhotic patients. An elevated extracellular concentration of valine could improve dendritic cell function in HCV cirrhotic patients. These data provide a rationale for nutrition therapy that could be beneficial to patients with cirrhosis.
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Report
(3 results)
Research Products
(13 results)
