| Project/Area Number |
16K08429
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
道具 伸也 福岡大学, 薬学部, 准教授 (60399186)
高田 芙友子 福岡大学, 薬学部, 助教 (70412575)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 血液脳関門 / serum amyloid A / 慢性閉塞性肺疾患 / 脳血管内皮細胞 / 脳ペリサイト / Serum amyloid A / サイトカイン / ケモカイン / 薬剤中枢性副作用 |
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| Outline of Final Research Achievements |
Serum levels of the serum amyloid A (SAA) were elevated in patients with acutely exacerbated COPD. The aim of this study is to determine the effect of SAA on brain microvascular endothelial cells and brain pericytes. We found that (1) brain endothelial barrier was impaired by apo-SAA, (2) apo-SAA increased mRNA expression levels of the pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Toll like receptor 4 (TLR4) is involved in the mechanisms by which apo-SAA induces mRNA expression of the IL-1β and IL-6 in brain pericytes. Based on these findings, SAA induces the hyperpermeability of brain endothelial cells and the increased inflammatory reactivity of brain pericytes; these direct and indirect actions of SAA contribute to COPD-induced BBB dysfunction.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、BBB構成細胞である脳血管内皮細胞および脳ペリサイトに対するSAAの作用を検討した。その結果、SAAが直接的および間接的経路を介して血液脳関門のバリア機能を低下させることが判った。今後は、COPD病態におけるSAA変動、BBB障害および脳ペリサイト病変化の関連性について追究し、脳ペリサイトの病変化を機軸にした「COPD病態進行とBBB障害」の連関機構を明らかにする必要がある。以上、本研究はCOPD病態におけるBBB機能障害発現の標的分子としてSAAを提示した点で意義深い。
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