2020 Fiscal Year Final Research Report
Development of a novel treatment for refractory asthma focusing on the control of fatty acid composition
Project/Area Number |
18K08168
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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 53030:Respiratory medicine-related
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Research Institution | University of Tsukuba |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Keywords | 喘息 / 脂肪酸 / Elovl6 |
Outline of Final Research Achievements |
We investigated the roles of Elovl6 in the development of allergic airway inflammation using mice deficient in Elovl6. The lungs of the OVA sensitized/challenged Elovl6 knockout mice accumulated myristic (14:0), palmitic (16:0) and palmitoleic (C16:1) fatty acids, and contained less stearic (C18:0) and oleic (C18:1) fatty acids. It was interesting that increased numbers of both eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF), elevated mRNA levels of IL-5, IL-6, IL-13 and IL-17A in the lungs, and severe inflammatory changes of the airway epithelium were observed in Elovl6 knockout mice with OVA treatment when compared with the corresponding WT mice. Enhanced goblet cell hyperplasia and elevated serum levels of OVA specific IgE were also detected in the OVA sensitized/challenged Elovl6-knockout mice.
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Free Research Field |
免疫・アレルギー性呼吸器疾患の病態生理
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Academic Significance and Societal Importance of the Research Achievements |
肥満と重症喘息に関する疫学的な研究が数多く存在する一方で、分子細胞生物学的な側面からアプローチした研究はきわめて少ない。これまでに行われた研究の多くは組織に蓄積する脂質の「量」に着目し、とくに喘息領域では生体内で合成されないω3やω6必須脂肪酸を中心に、それらの「摂取量」によってアレルギー性気道炎症が修飾されることが報告されている。これに対して本研究は、生体内で合成される脂肪酸を含めた脂質の「バランス」を包括的に捉え、その不均衡が難治性喘息をもたらす病態について明らかにするものである。
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