Development of Novel Therapeutic Medicines for Inflammatory Bowel Disease with Enhancement of IL-10 Production in Intestinal Macrophages
Project/Area Number |
18K06698
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47040:Pharmacology-related
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Research Institution | University of Toyama |
Principal Investigator |
Hayashi Shusaku 富山大学, 学術研究部薬学・和漢系, 助教 (10548217)
|
Project Period (FY) |
2018-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | 炎症性腸疾患 / 腸管マクロファージ / IL-10 / Fatty acid synthase / 再燃予防 / 粘膜治癒 / 上皮細胞 / IBD再燃モデル / DARTS / 長期寛解維持 / ベルベリン / 粘膜修復 / 腸管粘膜免疫系 |
Outline of Final Research Achievements |
We have proposed that the enhancement of interleukin (IL)-10 production in the intestinal macrophages has the potential to be a novel therapeutic mechanism for maintaining the remission of inflammatory bowel disease (IBD) and found berberine as a candidate compound for IL-10 enhancer. In the present study, we developed a useful experimental animal model to evaluate the relapse phase of IBD and investigated the effect of berberine on this model. Berberine significantly attenuated colitis symptoms during the relapse phase of IBD relapse model. Furthermore, we detected fatty acid synthase (FAS) as a candidate target protein. FAS inhibitor suppressed the IL-10 production of macrophages enhanced by berberine in a concentration-dependent manner. This study suggests that FAS activators such as berberine may be useful in developing a novel therapeutic strategy aimed at preventing relapse in IBD.
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Academic Significance and Societal Importance of the Research Achievements |
炎症性腸疾患(IBD)に対する治療薬開発は、過剰な炎症を抑制して寛解に導くことをコンセプトに行われてきたが、現在では再燃させることなく、長期間寛解を維持させることが最大の目標とされている。また、これまで有用なIBD再燃モデルは開発されておらず、候補薬物が再燃を予防し、長期寛解維持を実現するかの臨床予測性は困難であった。よって、本研究にて得られた成果は、IBD治療において選択肢の少ない寛解維持療法の開発研究を推進する波及効果が期待される。
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Report
(5 results)
Research Products
(16 results)