Investigation of new self-defense mechanism with innate immunity and glucocorticoid metabolizing enzyme

• Project/Area Number: 16K09792
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Hokkaido University
• Principal Investigator: SAI SHUJI 北海道大学, 遺伝子病制御研究所, 客員研究員 (50737872)
• Research Collaborator: Yamada Taisho ; Sato Seiichi ; Takaoka Akinori
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: グルココルチコイドホルモン代謝酵素 / 自然免疫 / サイトカインストーム / グルココルチコイドホルモン / インフルエンザウイルス / RIG-I / 11b-HSD / １１ｂ－HSD1 / グルココルチコイドホルモン代謝

Outline of Final Research Achievements

Innate immune receptor RIG-I, which senses influenza virus (Flu), produces interferon (IFN) to play a critical role for self-defense. Glucocorticoid hormones (GC) suppress abnormal activation of RIG-I. In this study we found the mechanism that intracellular GC metabolizing enzyme 11b-HSD1 suppressed RIG-I signaling. 11b-HSD1, which induced by Flu infection, converts inert GC to active GC suppressing IFN production. GC and RIG-I synergistically induced 11b-HSD1 and independently suppressed RIG-I signaling. There is a cross network and self-defense mechanism between innate immunity and GC signaling.

Academic Significance and Societal Importance of the Research Achievements

重症インフルエンザウイルス（Flu）感染では、サイトカインストームを合併すると、重篤な状態となる。グルココルチコイドホルモン（GC）は、サイトカイン産生を抑制する有効な治療薬である。本研究では、細胞内GC代謝酵素11b-HSD1が、特異的に過剰なサイトカイン産生を抑制することを見出した。この知見は、効率的なGC治療に有用であり、将来的に新たな治療薬の開発に寄与すると思われる。

Research Products

• [Journal Article] Peripheral glucocorticoid metabolism selectively modulates innate immune receptor RIG-I (2018)
  • Author(s): Sai Shuji、Yamada Taisho、Katsuyama Naoya、Takaoka Akinori
  • Journal Title: Endocrine Abstracts Volume: 59 Pages: 35-35
  • DOI: 10.1530/endoabs.59.p035
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Peripheral glucocorticoid metabolism selectively modulates innate immune receptor RIG-I (2018)
  • Author(s): Shuji Sai, Taisho Yamada, Naoya Katsuyama, Akinori Takaoka
  • Organizer: Society for Endocrinolgy BES 2018
  • Int'l Joint Research
• [Presentation] 自然免疫RIG-Iと11b-HSD1による新たな炎症制御機構の解明 (2017)
  • Author(s): 勝山直哉、齋秀二、山田大翔、高岡晃教
  • Organizer: 第25回日本ステロイドホルモン学会