A novel anti-inflammatory drug targeting purinergic receptors

• Project/Area Number: 22790088
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Tokyo University of Science
• Principal Investigator: TSUKIMOTO Mitsutoshi 東京理科大学, 薬学部・薬学科, 助教 (70434040)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 免疫学 / 薬学 / プリン受容体 / ATP / 炎症 / T細胞 / マクロファージ / 免疫 / P2X受容体 / P2Y受容体 / ATP受容体

Research Abstract

It is important to establish a novel target of anti-inflammatory drug because immune disease is increasing in all over the world. In this study, I found that P2X7 and P2Y6 purinergic receptors play an important role in activation of T cells and macrophages. The antagonists of these receptors significantly suppressed the increase of pro-inflammatory cytokine levels in sepsis model. I propose that the antagonists of P2X7 and P2Y6 receptors would be candidates of novel anti-inflamatory drug.

Research Products

• [Journal Article] Regulation of P2X7-dependent inflammatory functions by P2X4 receptor in mouse macrophages (2012)
  • Author(s): A. Kawano, M. Tsukimoto, D. Mori, T. Noguchi, H. Harada, T. Takenouchi, H. Kitani and S. Kojima
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 420(1) Pages: 102-7
  • Peer Reviewed
• [Journal Article] Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages (2012)
  • Author(s): A. Kawano, M. Tsukimoto, Taisei Noguchi, Noriyuki Hotta, Hitoshi Harada, Takato Takenouchi, Hiroshi Kitani, Shuji Kojima
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 419(2) Pages: 374-80
  • Peer Reviewed
• [Journal Article] Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages (2012)
  • Author(s): 月本光俊#、河野鮎美#、野口泰聖、堀田教之、原田均、竹之内敬人、木谷裕、小島周二(#共第一著者)
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 419巻2号 Issue: 2 Pages: 374-380
  • DOI: 10.1016/j.bbrc.2012.01.156
  • Peer Reviewed
• [Journal Article] Regulation of P2X7-dependent inflammatory functions by P2X4 receptor in mouse macrophages (2012)
  • Author(s): 月本光俊#、河野鮎美#、森大輔、野口泰聖、原田均、竹之内敬人、木谷裕、小島周二(#共第一著者)
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 420巻1号 Issue: 1 Pages: 102-107
  • DOI: 10.1016/j.bbrc.2012.02.122
  • Peer Reviewed
• [Journal Article] Adenosine A(2B) receptor antagonist suppresses differentiation to regulatory T cells without suppressing activation of T cells (2011)
  • Author(s): H. Nakatsukasa, M. Tsukimoto, H. Harada, S. Kojima
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 409(1) Pages: 114-9
  • Peer Reviewed
• [Journal Article] Adenosine A2B receptor antagonist suppresses differentiation to regulatory T cells without suppressing activation of T cells (2011)
  • Author(s): 月本光俊#、中司寛子#、原田均、小島周二(#共第一著者)
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 409 Issue: 1 Pages: 114-119
  • DOI: 10.1016/j.bbrc.2011.04.125
  • Peer Reviewed
• [Journal Article] Involvement of SLC17A9-Dependent Vesicular Exocytosis in the Mechanism of ATP Release During T Cell Activation (2010)
  • Author(s): A. Tokunaga, M. Tsukimoto, H. Harada, Y. Moriyama, and S. Kojima
  • Journal Title: The Journal of Biological Chemistry Volume: 285(23) Pages: 17046-17416
  • Peer Reviewed
• [Presentation] P2X7受容体依存性細胞死におけるP2X4受容体の関与 (2012)
  • Author(s): 河野鮎美、月本光俊、原田均、小島周二
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2012-03-29
• [Presentation] P2X7受容体を介した炎症反応におけるP2X4受容体の関与 (2011)
  • Author(s): 河野鮎美、月本光俊、原田均、小島周二
  • Organizer: 生理学研究所研究会『情報伝達物質としてのプリンの意義』
  • Place of Presentation: 生理学研究所(愛知県)
  • Year and Date: 2011-10-21
• [Presentation] P2X7受容体を介した炎症反応におけるP2X4受容体の関与 (2011)
  • Author(s): 河野鮎美、月本光俊、原田均、小島周二
  • Organizer: 情報伝達物質としてのプリンの意義(生理学研究所研究会)
  • Place of Presentation: 生理学研究所(愛知県)
  • Year and Date: 2011-10-21
• [Presentation] P2X7受容体を介した細胞死誘導におけるP2X4受容体の関与の検討 (2011)
  • Author(s): 河野鮎美、月本光俊、小島周二
  • Organizer: 第55回日本薬学会関東支部大会
  • Place of Presentation: 東邦大学(千葉県)
  • Year and Date: 2011-10-08
• [Presentation] マクロファージ活性化過程におけるATPシグナリングの関与 (2011)
  • Author(s): 榊隼人、月本光俊、小島周二
  • Organizer: 第55回日本薬学会関東支部大会
  • Place of Presentation: 東邦大学(千葉県)
  • Year and Date: 2011-10-08
• [Presentation] メサンギウム細胞におけるTGF-b誘発COX-2発現へのATPシグナリングの関与の検討 (2011)
  • Author(s): 中島隆文、月本光俊、小島周二
  • Organizer: 第55回日本薬学会関東支部大会
  • Place of Presentation: 東邦大学(千葉県)
  • Year and Date: 2011-10-08
• [Presentation] T細胞活性化過程におけるSLC17A9依存的小胞型ATP開口放出の関与 (2011)
  • Author(s): 月本光俊
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡市
• [Presentation] T細胞活性化における小胞型ATPエキソサイトーシスとP2受容体活性化の関与 (2010)
  • Author(s): 月本光俊
  • Organizer: 井上和秀教授 日本薬理学会江橋節郎賞受賞記念研究会「チャレンジングな創薬を目指した薬理学研究最前線」
  • Place of Presentation: 九州大学
  • Year and Date: 2010-05-07
• [Presentation] Blockade of murine T cell activation by antagonists of P2Y6 and P2X7 receptors. (2010)
  • Author(s): 月本光俊
  • Organizer: PURINES 2010 : Adenine nucleosides and nucleotides in Biomedicine
  • Place of Presentation: Tarragona-Barcelona, Spain