Role of IL-18 on blood pressure regulation

• Project/Area Number: 16K09643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Ehime University
• Principal Investigator: Takafumi Okura 愛媛大学, 医学系研究科, 寄附講座教授 (40260385)
• Research Collaborator: Miyoshi Ken-ichi ; Nagao Tomoaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 高血圧 / Interleukin-18 / NaCl-co-transporter / インターロイキン-18 / 血圧調節 / NaCl co-transporter / IL-18 / NaCl cotransport / インターロイキン18

Outline of Final Research Achievements

An increase in inflammatory cytokines is observed in hypertensive patients, which results in a further increase in blood pressure. We have reported that in Interleukin (IL)-18 deficient mice, even with induction of hypertension, the rise in blood pressure is mild. It is also reported that NaCl co-transporter (NCC) is one of the receptors for IL-18. Therefore, we considered that IL-18 might be involved in elevated blood pressure by activating NCC. However, in this study, it was not possible to clarify that activation of NCC is involved in blood pressure regulation.

Academic Significance and Societal Importance of the Research Achievements

高血圧患者では、血圧が高いだけでなく、様々な炎症性サイトカインが増加しており、動脈硬化促進に関与している。また、増加したサイトカインが直接血圧を上昇させることも知られている。本研究では、IL-18がNaCl-co-transporter (NCC) を介して、血圧調節に関与している可能性を考え研究を行った。本研究で、IL-18とNCCとの直接の関連性を明らかにすることはできなかったが、両者の関係が血圧に関連している可能性は極めて高く、今後のさらなる研究の発展が望まれる。

Research Products

• [Journal Article] AT2 receptor stimulation inhibits phosphate-induced vascular calcification (2019)
  • Author(s): Kukida M, Mogi M, Kan-No H, Tsukuda K, Bai HY, Shan BS, Yamauchi T, Higaki A, Min LJ, Iwanami J, Okura T, Higaki J, Horiuchi M
  • Journal Title: Kidney Int. Volume: 95 Issue: 1 Pages: 138-148
  • DOI: 10.1016/j.kint.2018.07.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neutralization of N-half osteopontin prevents atherosclerotic plaque rupture in ApoE-/- Mice (2018)
  • Author(s): Akiko Tanino, Takafumi Okura, Jun Irita, Tomoaki Nagao, Mie Kurata, Jun Suzuki, Masayoshi Kukida, Ken-ichi Miyoshi
  • Journal Title: Journal of Cardiology and Vascular Medicine Volume: 4 Pages: 1-10
  • Peer Reviewed
• [Presentation] アンジオテンシンII 2型(AT2)受容体刺激は LPSにより誘導される急性腎障害に対して保護的に働く (2018)
  • Author(s): 莖田昌敬, 大藏隆文, 長尾知明, 三好賢一, 檜垣彰典, 岩波純, 茂木正樹, 堀内正嗣, 檜垣實男
  • Organizer: 日本腎臓学会学術総会
• [Presentation] Interleukin-18投与マウスはNa+-CI-共輸送体の発現が増加し血圧が上昇する (2017)
  • Author(s): 谷野彰子、大蔵隆文，長尾知明，牧田愛祐，莖田昌敬，榎本大次郎，三好賢一，檜垣實男
  • Organizer: 第40回日本高血圧学会総会
• [Presentation] Osteopontin deficiency decreases autophagy and exacerbates tubular injury in acute kidney injury induced by folic acid (2017)
  • Author(s): Tomoaki Nagao, Takafumi Okura, Akiko Tanino,Ken-ichi Miyoshi, Masayoshi Kukida,Jitsuo Higaki
  • Organizer: AHA Council on Hypertension, American ：Society of Hypertension Joint Scientific Sessions
  • Int'l Joint Research