Regulatory mechanism of NLRP3 inflammasome in chronic inflammation

• Project/Area Number: 16H06270
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Osaka University
• Principal Investigator: Murakami Tomohiko 大阪大学, 歯学研究科, 講師 (50510723)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000); Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2016: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
• Keywords: 炎症 / インフラマソーム / NLRP3 / GNB1

Outline of Final Research Achievements

The NLRP3 inflammasome has been reported to be important for the development of chronic inflammation. However the regulatory mechanism of the NLRP3 inflammasome is not completely understood. In this study, we searched for new proteins that bind to NLRP3 by mass spectrometry and found G protein subunit beta 1 (GNB1). Functional analysis of GNB1 in NLRP3 inflammasome revealed that GNB1 negatively regulates NLRP3 inflammasome by suppressing the binding of NLRP3 to ASC.

Academic Significance and Societal Importance of the Research Achievements

本研究では、NLRP3インフラマソームを負に制御する新規因子であるGNB1を見出した。Gタンパク質とNLRP3インフラマソームの関連を示したことは新規性が高く、学術的にも重要である。さらにNLRP3インフラマソームが慢性炎症の発症に重要であることが判明していることから、GNB1によるNLRP3インフラマソームの抑制効果を利用することで、慢性炎症性疾患に対する新規治療法あるいは新規予防法のに応用できる可能性が考えられる。

Research Products

• [Journal Article] Cutting Edge: G Protein Subunit b 1 Negatively Regulates NLRP3 Inflammasome Activation (2019)
  • Author(s): Tomohiko Murakami, Lerdluck Ruengsinpinya, Eriko Nakamura,Yoshifumi Takahata, Kenji Hata, Hiroaki Okae,Shun’ichiro Taniguchi, Masafumi Takahashi and Riko Nishimura
  • Journal Title: The Journal of Immunology Volume: 202 Issue: 7 Pages: 1942-1947
  • DOI: 10.4049/jimmunol.1801388
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interaction of LEF1 with TAZ is necessary for the osteoblastogenic activity of Wnt3a (2018)
  • Author(s): Kida Jumpei、Hata Kenji、Nakamura Eriko、Yagi Hiroko、Takahata Yoshifumi、Murakami Tomohiko、Maeda Yoshinobu、Nishimura Riko
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 10375-10375
  • DOI: 10.1038/s41598-018-28711-4
  • Peer Reviewed / Open Access
• [Journal Article] 小胞体ストレスセンサーOASISによる骨形成制御 (2018)
  • Author(s): 村上智彦
  • Journal Title: THE BONE Volume: 32 Pages: 43-47
• [Journal Article] Transcriptional network systems in cartilage development and disease (2018)
  • Author(s): Nishimura Riko、Hata Kenji、Nakamura Eriko、Murakami Tomohiko、Takahata Yoshifumi
  • Journal Title: Histochem Cell Biol Volume: 149 Issue: 4 Pages: 353-363
  • DOI: 10.1007/s00418-017-1628-7
  • Peer Reviewed
• [Journal Article] Regulation of Cartilage Development and Diseases by Transcription Factors (2017)
  • Author(s): Nishimura Riko、Hata Kenji、Takahata Yoshifumi、Murakami Tomohiko、Nakamura Eriko、Yagi Hiroko
  • Journal Title: J Bone Metab Volume: 24 Issue: 3 Pages: 147-147
  • DOI: 10.11005/jbm.2017.24.3.147
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptional network controlling endochondral ossification (2017)
  • Author(s): Hata K, Takahata Y, Murakami T, Nishimura R
  • Journal Title: J Bone Metab Volume: 24 Issue: 2 Pages: 75-82
  • DOI: 10.11005/jbm.2017.24.2.75
  • Peer Reviewed / Open Access
• [Journal Article] 慢性炎症を基盤にした歯周疾患の病態の理解と治療戦略 (2016)
  • Author(s): 村上智彦
  • Journal Title: CLINICAL CALCIUM Volume: 26 Pages: 114-120
• [Presentation] 転写因子Sox4 はADAMTS4 およびADAMTS5 の発現を誘導して変形性関節症の発症に関与する (2018)
  • Author(s): 高畑佳史、中村恵理子、波多賢二、若林真、村上智彦、若森幹太、吉川浩史、松田昭生、福井尚志、西村理行
  • Organizer: 日本骨代謝学会学術集会
• [Presentation] Novel aspect of inflammatory molecule in articular cartilage destruction (2017)
  • Author(s): Tomohiko Murakami
  • Organizer: Bone Biology Forum
  • Invited
• [Presentation] 骨吸収を誘導する炎症性サイトカインIL-1bの産生に関わるインフラマソームの制御機構解析 (2016)
  • Author(s): 村上智彦、高畑佳史、波多賢二、西村理行
  • Organizer: 日本骨免疫学会
  • Place of Presentation: ホテルモントレ沖縄(沖縄県国頭郡)