| Project/Area Number |
18590977
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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 |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TSUKAMOTO Kazuhisa The University of Tokyo, Faculty of Medicine, Lecturer (20251233)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Masumi The University of Tokyo, Faculty of Medicine, Assist (70420213)
ISO-O Naoyuki The University of Tokyo, The institute of Medical Science, Assist (80420214)
WATANABE Takuro The University of Tokyo, Faculty of Medicine, Assist (20376437)
ISHIZAKA Nobukazu The University of Tokyo, Faculty of Medicine, Assist (20270879)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | macrophage / plant sterol / inflammation / cytokine / sterolin / atherosclerosis |
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| Research Abstract |
It has been known that the gene mutations in ABCG5 or ABCG8 result in phytosterolemia which is characterized with the premature atherosclerosis. However, the precise mechanism underlying in the atherogenesis in phytosterolemia has not been elucidated. In this study, we evaluated gene expressions of ABCG5 and ABCG8 in macrophages, and sterol-induced cytokine production in macrophages. Human macrophages, mouse peritoneal macrophages, J774. Al cells and RAW264.7 cells were utilized in this study. Neither ABCG5 nor ABCG8 were expressed in macrophages; even the cholesterol loading or stimulation with LXR agonist to the cells did not result in the expressions. The cells were loaded with cholesterol, sitosterol or campesterol in low (16 uM) and high (160 uM) concentrations, and cytokines production from the cells were examined. When the sterols were loaded to RAW264.7 cells in low concentration, sitosterol induced slight increase in cytokines in case they were stimulated with LPS. In high sterol loading with LPS stimulation, cholesterol induced prominent increase in cytokine production in both J774. Al cells and RAW264.7 cells, while sitosterol and campesterol reduced the production of cytokines. Due to the accidents of the animal facility of the Tokyo University, we could not perform sufficient animal experiments; however, the preliminary study revealed that the plasma total cholesterol levels and cytokine levels in the double knock out mice in apoE and sterolins might be lower than those of apoE deficient mice. These results indicate that the macrophages would not the main player in the atherogenesis of phytosterolemia. Through this study, we found that the splicing of ABCG5 cDNA in the liver is different from that in the intestine, which suggests that the sterolin 1 in the liver would behave differently from that in the intestine.
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