| Project/Area Number |
22K20886
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 炎症性腸疾患 / 鉄 / マクロファージ / ヒノキチオール |
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| Outline of Research at the Start |
炎症性腸疾患(Inflammatory Bowel Disease：IBD) などの慢性炎症性疾患では、炎症による細胞内鉄の過剰蓄積がマクロファージの炎症惹起能を亢進させ、さらに炎症を悪化させる。
本研究では鉄動態異常是正作用を持つHinokitiolが慢性炎症環境下での腸管マクロファージの炎症惹起能に与える影響を検証する。本研究を発展させる事で免疫抑制治療に依らない安全なIBD治療法の開発を目指す。
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| Outline of Final Research Achievements |
A trend toward decreased intracellular iron and inflammation-inducing capacity was observed when mouse macrophage cell lines were treated with Hinokitiol during LPS stimulation.
RNA-seq was also performed to elucidate the molecular mechanism by which the inflammatory potential of macrophages is reduced when intracellular iron is lowered, and changes in genes involved in intracellular metabolism such as glucose metabolism and oxidative phosphorylation were identified in the iron-chelated group. We focused on the AMPK pathway, which is upregulated in the iron-chelate group, and found that the inflammatory potential of the iron-chelate group was partially restored by the use of an AMPK inhibitor.
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| Academic Significance and Societal Importance of the Research Achievements |
今回Hinokitiolを用いた研究はin vitroでの検討までしか出来なかったが、マウスのマクロファージ細胞株でHinokitiolが抗炎症作用を発揮する可能性を確認できた。またマクロファージの細胞内鉄の多寡が糖代謝に影響を及ぼして炎症惹起能を調節しているメカニズムが示唆され、IBD治療の新たな切り口として開発できる可能性が示唆された。
今後、IBDモデルマウスを用いたin vivoの実験系においても、ヒノキチオールの抗炎症作用と安全性が検証出来れば、将来的に実臨床への応用の可能性も期待される。
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