Studies of modulation mechanisms of NF-kB signaling by novel cGMP pathway

• Project/Area Number: 16H05084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tohoku University
• Principal Investigator: Kurata Shoichiro 東北大学, 薬学研究科, 教授 (90221944)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: NF-kB / cGMP / 自然免疫 / NF-κB経路 / 薬学 / 遺伝学 / 免疫学

Outline of Final Research Achievements

Innate immunity is involved in chronic inflammatory diseases, cancer metastasis, and lifestyle diseases by recognition of self-ligands. Therefore, understanding of regulation mechanisms of innate immune system is indispensable for understanding of these diseases and drug discovery. We have identified novel cGMP signaling pathway that modulates NF-κB pathway in innate immunity. In this study, we investigated modulation mechanisms of NF-κB signaling by novel cGMP pathway.

Academic Significance and Societal Importance of the Research Achievements

自然免疫系が、病原体成分だけでなく、自己由来のリガンド（内因性リガンド）も認識することが明らかとなってきた。その際、病原体成分では強い反応が一過的に誘導されるのに対して、内因性リガンドでは弱い反応が持続的に誘導され、慢性炎症となる。したがって、このような自然免疫応答の違いが、どのようにして生じるのかを理解することが重要である。本研究により、自然免疫系の中心的なシグナル伝達であるNF-κB経路の調節機構が明らかとなり、自然免疫制御機構の理解に重要な進展が見られた。

Research Products

• [Int'l Joint Research] グラスゴー大学(英国)
• [Int'l Joint Research] グラスゴー大学(英国)
• [Journal Article] Unexpected role of the IMD pathway in Drosophila gut defense against Staphylococcus aureus (2018)
  • Author(s): Hori A, Kurata S, Kuraishi T
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 1 Pages: 395-400
  • DOI: 10.1016/j.bbrc.2017.11.004
  • NAID: 120006375092
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel mode of induction of the humoral innate immune response in Drosophila larvae (2017)
  • Author(s): Hiroyuki Kenmoku, Aki Hori, Takayuki Kuraishi, and Shoichiro Kurata
  • Journal Title: Disease Models & Mechanisms Volume: 10 Issue: 3 Pages: 271-281
  • DOI: 10.1242/dmm.027102
  • Peer Reviewed / Open Access
• [Journal Article] A subset of neurons controls the permeability of the peritrophic matrix and midgut structure in Drosophila adults. (2016)
  • Author(s): Hiroyuki Kenmoku, Hiroki Ishikawa, Manabu Ote, Takayuki Kuraishi, Shoichiro Kurata
  • Journal Title: J. Exp. Biol. Volume: 219 Pages: 2331-2339
  • DOI: 10.1242/jeb.122960
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Neural control of host resistance to ingested bacteria in Drosophila (2018)
  • Author(s): Shoichiro Kurata
  • Organizer: International Symposium for Infectious Diseases: Vector-borne Diseases
  • Int'l Joint Research / Invited
• [Presentation] Intestinal autophagy suppresses unnecessary damage response induced by non-pathogenic enteric bacteria through Ref(2)P regulation. (2018)
  • Author(s): Hiroki Nagai, Hiroshi Tatara, Shoichiro Kurata, Tamaki Yano
  • Organizer: 13th Japanese Drosophila Research Conference
  • Int'l Joint Research
• [Presentation] ショウジョウバエ腸管免疫の神経制御 (2018)
  • Author(s): 鈴木拓朗、石橋謙太朗、布施直之、倉田祥一朗
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] ショウジョウバエを用いた自然免疫の記憶機構の解析 (2018)
  • Author(s): 岡森千咲、布施直之、倉田祥一朗
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] Neural control of gut homeostasiss in Drosophila immunity (2017)
  • Author(s): Shoichiro Kurata
  • Organizer: The Tohoku Forum for Creativity Thematic Program 2017 New Horizons in Food Science via Agricultural Immunology
  • Int'l Joint Research / Invited
• [Presentation] ショウジョウバエ自然免疫における細菌認識と感染防御 (2017)
  • Author(s): 倉田祥一朗
  • Organizer: 第70回日本細菌学会九州支部総会、第54回日本ウイルス学会九州支部総会
  • Invited
• [Presentation] Neural control of gut homeostasiss in Drosophila immunity (2017)
  • Author(s): Shoichiro Kurata
  • Organizer: The 2017 Japan-NIH Joint Symposium
  • Place of Presentation: Sendai, Japan
  • Int'l Joint Research / Invited
• [Presentation] E3 ubiquitin ligase Sherpa mediates Toll innate immune signaling in Drosophila (2016)
  • Author(s): Takayuki Kuraishi, Kanoh Hirotaka, Li-Li Tong, Shoichiro Kurata
  • Organizer: 57th Annual Drosophila Research Conference
  • Place of Presentation: Florida, USA
  • Year and Date: 2016-07-13
  • Int'l Joint Research
• [Presentation] Neural control of gut homeostasiss in Drosophila immunity (2016)
  • Author(s): Shoichiro Kurata
  • Organizer: The 2nd Asian Invertebrate Immunology Symposium
  • Place of Presentation: Hangzhou, China
  • Int'l Joint Research / Invited
• [Presentation] 昆虫の自然免疫を支える異物パターン認識 (2016)
  • Author(s): 倉田祥一朗
  • Organizer: 日本比較免疫学会第28回学術集会
  • Place of Presentation: 東京
• [Remarks] 東北大学大学院薬学研究科生命機能解析学分野
  • URL: http://www.pharm.tohoku.ac.jp/~seimei/seimei_original.html