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Development of a novel treatment for refractory asthma focusing on the control of fatty acid composition

Research Project

Project/Area Number 18K08168
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Morishima Yuko  筑波大学, 医学医療系, 准教授 (10375511)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords喘息 / 脂肪酸 / Elovl6 / アレルギー性気道炎症 / 長鎖脂肪酸伸長酵素 / 脂肪酸組成
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.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018

All Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Elovl6欠損による肺組織の脂肪酸組成の変化がアレルギー性気道炎症を増悪させる.2020

    • Author(s)
      吉田和史,森島祐子,櫻井啓文,大澤 翔、矢﨑 海、Mingma Sherpa, 中嶋真之,松山政史,際本拓未,松野洋輔,石井幸雄,檜澤伸之.
    • Organizer
      第60回日本呼吸器学会学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Deletion of elongation of very long chain fatty acids family member 6 (Elovl6) enhances OVA-induced type 2 and non-type 2 allergic airway inflammation in mice.2020

    • Author(s)
      Yoshida K, Morishima Y, Sakurai H, Osawa H, Yazaki K, Mingma S, Nakajima M, Matsuyama M, Kiwamoto T, Matsuno Y, Ishii Y, Hizawa N.
    • Organizer
      第68回 日本アレルギー学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Enhanced Type 2 and non-Type 2 allergic airway inflammation in Elovl6-deficient mice.2020

    • Author(s)
      Yoshida K, Morishima Y, Sakurai H, Osawa H, Yazaki K, Mingma S, Nakajima M, Matsuyama M, Kiwamoto T, Matsuno Y, Ishii Y, Hizawa N. Enhanced Type 2 and non-Type 2 allergic airway inflammation in Elovl6-deficient mice.
    • Organizer
      American Thoracic Society Conference 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肺組織脂肪酸組成の変化がアレルギー性気道炎症に与える影響 -長鎖脂肪酸伸長酵素(Elovl6)に注目して.2019

    • Author(s)
      吉田和史,森島祐子,櫻井啓文,Mingma Sherpa, 中嶋真之,角田義弥,松山政史,際本拓未,松野洋輔,石井幸雄,檜澤伸之.
    • Organizer
      第59回 日本呼吸器学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 動物モデルを用いた炎症性呼吸器疾患の病態生理の解明.2019

    • Author(s)
      森島祐子.
    • Organizer
      第59回 日本呼吸器学会学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Elovl6欠損による肺組織脂肪酸組成変化とアレルギー性気道炎症増悪の関連.2019

    • Author(s)
      吉田和史,森島祐子,櫻井啓文,中嶋真之,松山政史,際本拓未,松野洋輔,石井幸雄,檜澤伸之.
    • Organizer
      第68回 日本アレルギー学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Deletion of Elovl6 alters fatty acid composition in lung tissue and enhances allergic airway inflammation.2019

    • Author(s)
      K. Yoshida, Y. Morishima, H. Sakurai, M. Sherpa, Y. Tsunoda, M. Nakajima, M. Matsuyama, T. Kiwamoto, Y. Matsuno, Y. Ishii, N. Hizawa.
    • Organizer
      2019 International Conference of American Thoracic Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] アレルギー性気道炎症における長鎖脂肪酸伸長酵素Elovl6の役割2019

    • Author(s)
      吉田和史、森島祐子、櫻井啓文、角田義弥、中嶋真之、松山政史、際本拓未、松野洋輔、石井幸雄、檜澤伸之
    • Organizer
      日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] The Role of Elongation of Very Long Chain Fatty Acids Family Member 6 (Elovl6) in Allergic Airway Inflammation2018

    • Author(s)
      K. Yoshida, Y. Morishima, H. Sakurai, Y. Tsunoda, M. Nakajima, M. Matsuyama, T. Kiwamoto, Y. Matsuno, Y. Ishii, N. Hizawa
    • Organizer
      International Conference of American Thoracic Society
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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