| Project/Area Number |
18K16406
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55030:Cardiovascular surgery-related
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| Research Institution | Kurume University |
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Principal Investigator |
Kanamoto Ryo 久留米大学, 医学部, 助教 (70817353)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | Syk / 腹部大動脈瘤 / B細胞 / 免疫グロブリン / Spleen Tyrosine Kinase / γグロブリン / IL-6 / MMP / マクロファージ / 大動脈瘤 / 外科 |
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| Outline of Final Research Achievements |
In this study, we aimed to investigate the role of Syk in human abdominal aortic aneurysm (AAA) pathogenesis using human AAA tissue. Immunohistochemical analysis showed infiltration of B cells, T cells, and macrophages in AAA samples. Syk activation was localized mainly in B cells and part of macrophages. AAA tissue in culture secreted IL-6, MMP-9, and MMP-2 without any stimulation. Secretions of IL-6 and MMP-9 were enhanced by exogenous normal human immunoglobulin G (IgG), which was suppressed by Syk inhibitor, whereas secretion of MMP-2 was insensitive to IgG or Syk inhibitor.The unstimulated secretions of IL-6, MMP-9, and MMP-2 were insensitive to Syk inhibitor. These results demonstrate an important role of Syk for IgG-dependent inflammatory response in human AAA.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果は、ヒト大動脈瘤組織の炎症および組織破壊活性がIgGによって調節され、それがSyk活性に依存することを示唆した。 本研究は腹部大動脈瘤の病態解明に有意なとともに、今後の研究で、内因性IgGも同様にSyk依存性に大動脈瘤病態に関与するか、ヒト大動脈瘤におけるSykの活性化を明らかとすることで、Sykは有望な薬物標的分子となりうると考える。腹部大動脈瘤に対するSyk阻害療法の臨床応用が期待される。
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