| Project/Area Number |
19K08637
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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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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 炎症 / IL-38 / サイトカイン / 炎症性肺疾患 / 肺癌 / 喘息 / 補体 |
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| Outline of Research at the Start |
炎症性サイトカインIL-1ファミリー、とりわけIL-18とIL-38がIL-17A,IL-36シグナルや補体を活性化し、好酸球炎症だけでなく、好中球炎症にも関与しているという作業仮説を持った。本研究では、IL-18, IL-38と補体の制御による炎症性肺疾患（気管支喘息とCOPD)の治療の研究を行う。
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| Outline of Final Research Achievements |
Interleukin (IL)-38 was discovered in 2001 and is a member of the IL-1 family of cytokines. IL-38 shows anti-inflammatory activity in several inflammatory diseases. We reported that IL-38 may enhance airway eosinophilic inflammation in asthma through IL-5 induction. We demonstrated that high IL-38 expression in tumor cells was significantly associated with reduction of CD8(+) TILs and tumor progression. These results suggest that IL-38 could be a therapeutic target for lung cancer. The IL-38 mRNA and protein expression were enhanced in the active mucosa of ulcerative colitis (UC), but not in Crohn's disease. DSS-colitis was significantly exacerbated in IL-38KO mice compared to wild type mice. IL-38 may play an anti-inflammatory and protective role in the pathophysiology of IBD, in particular ulcerative colitis, through the suppression of IL-36-induced inflammatory responses.
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| Academic Significance and Societal Importance of the Research Achievements |
喘息、癌、炎症性腸疾患の克服は大きな課題である。。本研究では、これら疾患におけるサイトカインIL-38と炎症の制御を研究した。マウス喘息モデル、坦がん(tumor bearing)モデルとDextran sulfate sodium(DSS)で誘導した炎症性腸疾患モデルでサイトカインIL-38は炎症を制御することを示した。サイトカインの制御は喘息、癌、炎症性腸疾患の治療に応用できると考えられた。
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