Regulation of inflammatory responses by food-derived compounds

• Project/Area Number: 24580177
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Nagoya University
• Principal Investigator: SHIBATA Takahiro 名古屋大学, 生命農学研究科, 助教 (80447838)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 自然免疫 / Toll様受容体 / 食品成分 / 炎症 / toll様受容体 / 自然炎症

Outline of Final Research Achievements

Toll-like receptors (TLRs) have been implicated in the pathogenesis of chronic inflammatory diseases. In this study, based on an extensive screening of vegetable extracts for TLR-inhibiting activity, we found cabbage extracts to be the richest sources of a TLR signaling inhibitor. We performed activity-guiding separation of the principal inhibitors and identified iberin from the cabbage. In addition, it was revealed that iberin specifically acted on the dimerization step of TLRs in the TLR signaling pathway. Moreover, we developed a novel probe combining an isothiocyanate-reactive group and an alkyne functionality for click chemistry and detected the probe bound to the TLRs in living cells, suggesting that iberin disrupts dimerization of the TLRs via covalent binding. These findings establish the TLR dimerization step as a target of food-derived anti-inflammatory compounds.

Research Products

• [Journal Article] Toll-like receptors as a target of food-derived anti-Inflammatory compounds. (2014)
  • Author(s): Shibata, T., Nakashima, F., Honda, K., Lu, Y. J., Kondo, T., Ushida, Y., Aizawa, K., Suganuma, H., Oe, S., Tanaka, H., Takahashi, T. and Uchida, K.
  • Journal Title: J. Biol. Chem. Volume: 289 Pages: 32757-32772
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 炎症応答における細胞膜コレステロールの関与 (2014)
  • Author(s): 中島史恵, 柴田貴広, 内田浩二
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学 生田キャンパス
• [Presentation] 血清アルブミンによるコレステロール引き抜きに伴う炎症誘導 (2013)
  • Author(s): 中島史恵, 柴田貴広, 内田浩二
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
• [Presentation] ニンニク抽出物に含まれるTLR阻害物質の探索
  • Author(s): 柴田貴広、盧育章、本多和也、河合慶親、内田浩二
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学
• [Presentation] キャベツ由来イソチオシアネートのTLR抑制機構
  • Author(s): 本多和也、柴田貴広、河合慶親、田中浩士、高橋孝志、牛田悠介、相澤宏一、稲熊隆博、内田浩二
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学
• [Presentation] たまねぎ抽出物に含まれるTLR抑制物質の同定と作用機序解析
  • Author(s): 柴田貴広、中島史恵、本多和也、河合慶親、牛田悠介、相澤宏一、稲熊隆博、内田浩二
  • Organizer: 日本農芸化学会2013年度大会
  • Place of Presentation: 東北大学