Elucidating the molecular bases and pathophysiological significances of the extracellular inflammasome which drives chronic inflammation

• Project/Area Number: 15H06785
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Shujitsu University
• Principal Investigator: Watanabe Masahiro 就実大学, 薬学部, 助教 (10758246)
• Research Collaborator: MORI Shuji 就実大学, 薬学部, 教授 (50220009) ; TOYOMURA Takao 就実大学, 薬学部, 講師 (40425137)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 慢性炎症 / HMGB1 / 終末糖化産物 / AGEs / サイトカイン

Outline of Final Research Achievements

To elucidate the mechanisms that HMGB1 or advanced glycation endproducts (AGEs) induce chronic inflammation, we searched for interaction partners of these molecules and investigated the effects induced by the interaction of the molecules. We found that AGEs directly interact with a cytokine, TWEAK. Furthermore, using cellular model, it was shown that AGEs inhibited function of TWEAK which regulate TNFα-stimulated inflammatory reactions. These results suggested that AGEs induce chronic inflammation through inhibiting function of the cytokines which regulate inflammatory reactions.

Research Products

• [Journal Article] Advanced glycation end products attenuate the function of tumor necrosis factor-like weak inducer of apoptosis to regulate the inflammatory response (2017)
  • Author(s): Watanabe M, Toyomura T, Wake H, Liu K, Teshigawara K, Takahashi H, Nishibori M, Mori S
  • Journal Title: Molecular and Cellular Biochemistry Volume: 印刷中 Issue: 1-2 Pages: 153-162
  • DOI: 10.1007/s11010-017-3045-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Damps関連サイトカインの機能に対するAGEsの影響 (2016)
  • Author(s): 渡邊政博，豊村隆男，和氣秀徳，劉克約，勅使川原匡，高橋英夫，西堀正洋，森秀治
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター／東北大学川内北キャンパス（宮城県仙台市）
  • Year and Date: 2016-09-25
• [Presentation] AGEs 共存による Damps 関連サイトカイン類の機能変化 (2016)
  • Author(s): 渡邊政博，豊村隆男，和氣秀徳，劉克約，勅使川原匡，高橋英夫，西堀正洋，森秀治
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-26
• [Presentation] AGEsとTNF関連サイトカインとの相互作用部位の解析 (2016)
  • Author(s): 渡邊政博，豊村隆男，和氣秀徳，劉克約，勅使川原匡，高橋英夫，西堀正洋，森秀治
  • Organizer: 第26回 創薬・薬理フォーラム
  • Place of Presentation: 岡山大学医学部（岡山県岡山市）
• [Presentation] HMGB1と相互作用するサイトカインに対するAGEsの影響 (2015)
  • Author(s): 渡邊政博，豊村隆男，和氣秀徳，劉克約，勅使川原匡，高橋英夫，西堀正洋，森秀治
  • Organizer: BMB2015 第38回日本分子生物学会，第88回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド（神戸ポートピアホテル，神戸国際会議場，神戸国際展示場，神戸商工会議所）（兵庫県神戸市）
  • Year and Date: 2015-12-01