Molecular analysis of intestinal stress induction and regulation of the stress by food factors

• Project/Area Number: 20248013
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: The University of Tokyo
• Principal Investigator: SHIMIZU Makoto The University of Tokyo, 大学院・農学生命科学研究科, 教授 (30114507)
• Co-Investigator(Renkei-kenkyūsha): TOTSUKA Mamoru 東京大学, 大学院・農学生命科学研究科, 准教授 (70227601) ; SATSU Hideo 東京大学, 大学院・農学生命科学研究科, 助教 (80323484)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥47,580,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥10,980,000); Fiscal Year 2010: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000); Fiscal Year 2009: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000); Fiscal Year 2008: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000)
• Keywords: 腸管上皮細胞 / 炎症モデル / 複合培養 / 抗ストレス作用

Research Abstract

Inflammatory reactions induced by various stresses in the intestinal epithelium were investigated from the viewpoint of cell-cell interaction. Interaction between intestinal epithelial cells and immune cells was analyzed using in vitro cell culture model systems newly constructed in this study. Food substances that could suppress inflammatory reactions were also searched using these systems. Activated macrophages and mast cells induced damage to epithelial cells, whereas epithelial cells induced differentiation and functional activation of mast cells. Certain molecules responsible for the cell-cell interactions and food factors with anti-inflammatory functions were successfully found.

Research Products

• [Journal Article] IEX-1 suppressed apoptotic damage in human intestinal epithelial Caco-2 cells induced by coculturing with macrophage-like THP-1 cells (2011)
  • Author(s): Ishimoto Y., Satsu H., Totsuka M., Shimizu, M.
  • Journal Title: Biosci.Rep. 31 Pages: 345-351
  • Peer Reviewed
• [Journal Article] Synergistic effect of tumore necrosis factor-alpha and hydrogen peroxide on the induction of IL-8 production in human intestinal Caco-2 cells. (2011)
  • Author(s): Shin H.S., Zhao Z., Satsu H., Totsuka M., Shimizu M.
  • Journal Title: Inflammation Volume: (掲載確定)
  • Peer Reviewed
• [Journal Article] IEX-1 suppressed apoptotic damage in human intestinal epithelial Caco-2 cells induced by coculturing with macrophage-like THP-1 cells. (2011)
  • Author(s): Ishimoto Y., Satsu H., Totsuka M, Shimizu M.
  • Journal Title: Biosci.Rep Volume: (掲載確定)
  • Peer Reviewed
• [Journal Article] In vitro analysis of the interaction between human intestinal epithelial cells and macrophage-like cells (2010)
  • Author(s): Ishimoto Y., Satsu H., Mochizuki T., Totsuka M., Shimizu M.
  • Journal Title: Animal Cell Technology : Basic and Applied Aspects 16 Pages: 231-236
  • Peer Reviewed
• [Journal Article] Transient up-regulation of immunity- and apoptosis- related genes in Caco-2 cells cocultured with THP-1 cells evaluated by DNA microarray analysis (2010)
  • Author(s): Ishimoto Y., Nakai Y., Satsu H., Totsuka M., Shimizu M.
  • Journal Title: Biosci.Biotechnol.Biochem 74 Pages: 437-439
  • NAID: 10027551976
  • Peer Reviewed
• [Journal Article] Disaccharide derived from chondroitin sulfate A suppressed CpG-induced IL-6 secretion in macrophage-like J774.1 cells (2010)
  • Author(s): Jin M., Iwamoto T., Yamada K., Satsu H., Totsuka M., Shimizu M.
  • Journal Title: Cytokine 51 Pages: 53-59
  • Peer Reviewed
• [Journal Article] Transient up-regulation of immunity-and apoptosis-related genes in Caco-2 cells cocultured with THP-1 cells evaluated by a DNA microarray analysis. (2010)
  • Author(s): Ishimoto Y., Nakai Y., Satsu H, Totsuka M., Shimizu M.
  • Journal Title: Biosci.Biotechnol.Biochem. Volume: 74 Pages: 437-439
  • NAID: 10027551976
  • Peer Reviewed
• [Journal Article] Disaccharide derived from chondroitin sulfate A suppressed CpG-induced IL-6 secretion in macrophage-like J774.1 cells. (2010)
  • Author(s): Jin M., Iwamoto T., Yamada K., Satsu H., Totsuka M., Shimizu M.
  • Journal Title: Cytokine Volume: 51 Pages: 53-59
  • Peer Reviewed
• [Journal Article] Transient up-regulation of immunity-and apoptosis-related genes in Caco-2 cells cocultured with THP-1 cells evaluated by a DNA microarray analysis. (2010)
  • Author(s): Ishimoto, Y, Nakai, Y, Satsu, H, Totsuka, M, Shimizu, M.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry 74 Pages: 437-439
  • NAID: 10027551976
  • Peer Reviewed
• [Journal Article] In vitro analysis of the interaction between human intestinal epithelial cells and macrophage-like cells. (2010)
  • Author(s): Ishimoto, Y., Satsu, H., Mochizuki, T., Totsuka, M., Shimizu, M.
  • Journal Title: Animal Cell Technology : Basic and Applied Aspects 16(印刷中)
  • Peer Reviewed
• [Journal Article] Dietary taurine attenuates dextran sulfate sodium (DSS)-induced experimental colitis in mice (2009)
  • Author(s): Shimizu M., Zhao Z., Ishimoto Y., Satsu H.
  • Journal Title: Advances in Experimental Medicine and Biology 643 Pages: 265-271
  • Peer Reviewed
• [Journal Article] Protective effect of quercetin on ER stress caused by calcium dynamics dysregulation in intestinal epithelial cells (2009)
  • Author(s): Natsume Y., Ito S., Satsu H., Shimizu M.
  • Journal Title: Toxicology 258 Pages: 164-175
  • Peer Reviewed
• [Journal Article] 腸管上皮の炎症抑制作用を持つアミノ酸・ペプチド (2009)
  • Author(s): 清水誠
  • Journal Title: Functional Food 3 Pages: 95-99
• [Journal Article] Suppressive effect of an isoflavone fraction on tumor necrosis factor-α-induced interleukin-8 produciton in human intestinal epithelial Caco-2 cells (2009)
  • Author(s): Satsu H., Hyun J.S., Shin H.S., Shimizu M.
  • Journal Title: J.Nutr.Sci.Vitaminol. 55 Pages: 442-446
  • Peer Reviewed
• [Journal Article] Dietary taurine attenuates dextran sulfate sodium (DSS)-induced experimental colitis in mice. (2009)
  • Author(s): Shimizu, M., Zhao, Z., Ishimoto, Y., Satsu, H.
  • Journal Title: Advances in Experimental Medicine and Biology 643 Pages: 265-271
  • Peer Reviewed
• [Journal Article] Protective effect of quercetin on ER stress caused by calcium dynamics dysregulation in intestinal epithelial cells. (2009)
  • Author(s): Natsume, Y., Ito, S., Satsu, H., Shimizu, M.
  • Journal Title: Toxicology 258 Pages: 164-175
  • Peer Reviewed
• [Journal Article] Suppressive effect of an isoflavone fraction on tumor necrosis factor-α-induced interleukin-8 production in human intestinal epithelial Caco-2 cells. (2009)
  • Author(s): Satsu, H, Hyun, Ja Shil, Shin, Hee Soon, Shimizu, M.
  • Journal Title: Journal of Nutritional Science & Vitaminology 55 Pages: 442-446
  • NAID: 10025972267
  • Peer Reviewed
• [Journal Article] Synergistic effect of tumor necrosis factor-alpha and hydrogen peroxide on the induction of IL-8 production in human intestinal Caco-2 cells
  • Author(s): Shin H.S., Zhao, Z., Satsu, H., Totsuka, M., Shimizu, M.
  • Journal Title: Inflammation (in press)
  • Peer Reviewed
• [Journal Article] In vitro analysis of the interaction between human intestinal epithelial cells and macrophage-like cells.
  • Author(s): Ishimoto, Y., Satsu, H., Mochizuki, T., Totsuka, M., Shimizu, M.,
  • Journal Title: Animal Cell Technology (in press)
  • Peer Reviewed
• [Presentation] 複合培養系を用いたマスト細胞と腸管上皮細胞の相互作用解析 (2011)
  • Author(s): 田中大季、望月鉄之祐、清水誠
  • Organizer: 日本農芸化学会2011年度大会
  • Place of Presentation: 京都女子大学(京都)
• [Presentation] クロロゲン酸及びコーヒー酸による抗炎症作用とその機構解析 (2011)
  • Author(s): 申喜淳、薩秀夫、戸塚護、清水誠
  • Organizer: 日本農芸化学会2011年度大会
  • Place of Presentation: 京都女子大学(京都)
• [Presentation] 腸管上皮細胞とマスト細胞のin vitroにおける相互作用の解析 (2010)
  • Author(s): 望月鉄之祐、田中大季、薩秀夫、戸塚護、清水誠
  • Organizer: 日本農芸化学会関東支部2010年度大会
  • Place of Presentation: 千葉大学(千葉)
  • Year and Date: 2010-10-09
• [Presentation] 腸管上皮細胞とマスト細胞のin vitroにおける相互作用の解析 (2010)
  • Author(s): 望月鉄之祐、田中大季、薩秀夫、戸塚護、清水誠
  • Organizer: 日本農芸化学会関東支部2010年度大会(千葉)
  • Place of Presentation: 千葉大学(千葉)
  • Year and Date: 2010-10-09
• [Presentation] ストレスが誘導するアレルギー性の腸炎症モデルの構築 (2010)
  • Author(s): 松川あゆみ、吉田綾子、清水誠、戸塚護
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-03-29
• [Presentation] 腸管上皮細胞においてTLRリガンドで誘導されるサイトカイン産生に対するスフィンゴシン-1-リン酸の作用とその機構解析 (2010)
  • Author(s): 岩本拓、戸塚護、清水誠、薩秀夫
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-03-29
• [Presentation] マクロファージ様細胞との複合培養により腸管上皮細胞が受ける障害の機構解析 (2010)
  • Author(s): 石本容子、薩秀夫、望月鉄之祐、戸塚護、清水誠
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-03-29
• [Presentation] ゲラニインがマウス小腸上皮細胞株のToll様受容体リガンド刺激で誘導されるインターロイキン6産生に与える影響 (2010)
  • Author(s): 尾形悠、岩本拓、伊東秀之、波多野力、清水誠、戸塚護
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-03-29
• [Presentation] マクロファージ様細胞との複合培養により腸管上皮細胞が受ける傷害の機構解析 (2010)
  • Author(s): 石本容子、薩秀夫、望月鉄之祐、戸塚護、清水誠
  • Organizer: 日本農芸化学会2010年度大会
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-03-29
• [Presentation] 腸管上皮細胞における炎症と食品成分によるその制御 (2010)
  • Author(s): 清水誠
  • Organizer: 金沢大学薬学シンポジウム
  • Place of Presentation: 金沢大学(金沢)(特別講演)
  • Year and Date: 2010-02-12
• [Presentation] 腸管上皮細胞における炎症と食品成分によるその制御 (2010)
  • Author(s): 清水誠
  • Organizer: 金沢大学薬学シンポジウム(特別講演)
  • Place of Presentation: 金沢大学(金沢)
  • Year and Date: 2010-02-12
• [Presentation] Construction of a co-culture model to analyze the interaction between human mast cells (HMC-1) and intestinal epithelial cells (Caco-2) (2010)
  • Author(s): Tanaka D., Mochizuki T., Satsu H., Totsuka M., Shimizu M.
  • Organizer: International Meeting of Japanese Association of Animal Cell Technology (JAACT2010)
  • Place of Presentation: 北海道大学(札幌)
• [Presentation] Construction of a co-culture model to analyze the interaction between human mast cells (HMC-1) and intestinal epithelial cells (Caco-2) (2010)
  • Author(s): Tanaka D., Mochizuki T., Satsu H., Totsuka M., Shimizu M.
  • Organizer: International Meeting of Japanese Association of Animal Cell Technology (JAACT2010)
  • Place of Presentation: 北海道大学(北海道)
• [Presentation] 食品による腸管機能の制御と機能性食品 (2009)
  • Author(s): 清水誠
  • Organizer: 第3回食品薬学シンポジウム
  • Place of Presentation: 近畿大学(大阪)(特別講演)
  • Year and Date: 2009-11-12
• [Presentation] 食品による腸管機能の制御と機能性食品 (2009)
  • Author(s): 清水誠
  • Organizer: 第3回食品薬学シンポジウム(特別講演)
  • Place of Presentation: 近畿大学(大阪)
  • Year and Date: 2009-11-12
• [Presentation] 腸管上皮細胞のサイトカイン産生に対するスフィンゴシン-1-リン酸の作用 (2009)
  • Author(s): 岩本拓、戸塚護、清水誠、薩秀夫
  • Organizer: セラミド研究会
  • Place of Presentation: 北海道大学(札幌)
  • Year and Date: 2009-11-06
• [Presentation] 炎症刺激による腸管上皮IL-8産生亢進に対するクロロゲン酸およびコーヒー酸の抑制作用機構の解析 (2009)
  • Author(s): 申喜淳、薩秀夫、戸塚護、清水誠
  • Organizer: 日本農芸化学会関東支部2009年度大会
  • Place of Presentation: 玉川大学(東京)
  • Year and Date: 2009-10-31
• [Presentation] Role of functional food factors for intestinal immune function (2009)
  • Author(s): 清水誠
  • Organizer: 2^<nd> Italy-Japan Symposium on Food and Health : past, present and future
  • Place of Presentation: 日伊会館(東京)(invited lecture)
  • Year and Date: 2009-10-22
• [Presentation] Role of functional food factors for intestinal immune function. (2009)
  • Author(s): Shimizu, M
  • Organizer: 2^<nd> Italy-Japan Symposium on Food and Health : past, present and future(招待講演)
  • Place of Presentation: 日伊会館(東京)
  • Year and Date: 2009-10-22
• [Presentation] Toll様受容体刺激した腸管上皮細胞からのIL-8産生に対するカルノシンの産生調節作用 (2009)
  • Author(s): 丸山裕美、孫動玉、薩秀夫、戸塚護、清水誠
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: マリンメッセ福岡(福岡)
  • Year and Date: 2009-03-29
• [Presentation] Toll様受容体刺激した腸管上皮細胞からのIL-8産生に対するカルノシンの産生調節作用 (2009)
  • Author(s): 丸山裕美、孫動玉、薩秀夫、戸塚護、清水誠、
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-29
• [Presentation] In vitro analysis of e interactioetween man intestinal epithelial cells and macrophage-like cells (2008)
  • Author(s): Ishimoto Y., Satsu H., Mochizuki T., Totsuka M., Shimizu M.
  • Organizer: 2008 International Meeting of Japanese Association for Animal Cell Technology(JAACT2008)
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2008-11-27
• [Presentation] In vitro analysis of the interaction between human intestinal epithelial cells and macrophage-like cells (2008)
  • Author(s): Ishimoto, Y., Satsu, H., Mochizuki, T., Totsuka, M., Shimizu, M
  • Organizer: 2008 International Meeting of Japanese Association for Animal Cell Technology (JAACT2008)
  • Place of Presentation: 福岡
  • Year and Date: 2008-11-27
• [Presentation] 炎症刺激による腸管上皮IL-8産生亢進に対するクロロゲン酸の抑制作用-機構解析と構造活性相関 (2008)
  • Author(s): 申喜淳、趙朝輝、薩秀夫、戸塚護、清水誠
  • Organizer: 日本食品免疫学会第4回学術会議(JAFI2008)
  • Place of Presentation: こまばエミナース(東京)
  • Year and Date: 2008-05-13
• [Presentation] 炎症刺激による腸管上皮IL-8産生亢進に対するクロロゲン酸の抑制作用-機構解析と構造活性相関 (2008)
  • Author(s): 申喜淳、趙朝輝、薩秀夫、戸塚護、清水誠
  • Organizer: 日本食品免疫学会2008年度大会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-13