| Project/Area Number |
18K15049
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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 48040:Medical biochemistry-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 喘息 / モデルマウス / IL-33 / シグナル伝達 |
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| Outline of Final Research Achievements |
Asthma is an allergic disease associated with airway inflammation. Activated type 2 innate lymphoid cells (ILC2) by interleukin (IL)-33 produce IL-5 and IL-13, which induce airway inflammation. The kinases MK2 and MK3, are downstream substrates of p38MAPK pathway involved in IL-33 signaling, play a key role of proinflammatory cytokine production including IL-5 and IL-13. In this study, we investigated the involvement of MK2 and MK3 in the pathogenesis of asthma using knockout mice. Wild-type and MK3-knockout mice showed typical airway inflammation. On the other hand, MK2-knockout mice showed mild airway inflammation due to lack of activation of lung ILC2 and suppression of IL-5 and IL-13 production. These results indicate that MK2 is involved in the development of airway inflammation in asthma.
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| Academic Significance and Societal Importance of the Research Achievements |
喘息の発症に関わるサイトカインIL-5とIL-13の産生は、肺ILC2におけるIL-33シグナルのp38経路により誘導される。本研究は、p38経路のリン酸化酵素MK2およびMK3の遺伝子欠損マウスを用いた喘息モデルにより、p38-MK3経路ではなく、p38-MK2経路がIL-5とIL-13の産生において不可欠な経路であることを明らかにした。本研究の成果は、MK2自身およびp38-MK2 経路の下流シグナル分子が喘息治療の新たな標的になる可能性を示し、今後の治療法開発の分子基盤になるものと期待される。
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