Mechanisms of a failure in the intestinal homeostasis and its regulation by food

• Project/Area Number: 19780104
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Food science
• Research Institution: Nihon University
• Principal Investigator: TAKAHASHI Kyoko Nihon University, 生物資源科学部, 講師 (70366574)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,590,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: 腸管上皮細胞 / マスト細胞 / 腸内細菌 / tollUke receptor / 遺伝子発現 / toll like receptor / 透過性

Research Abstract

腸管の恒常性の破綻に関与する過程として、腸管上皮細胞の腸内共生菌に対する過剰応答、マスト細胞の活性化の2つに着目した。前者に関しては、微生物菌体の認識に関わる分子の腸管上皮細胞特異的な転写制御機構の一端を明らかにし、後者についてはマスト細胞のアレルギー応答が菌体成分を認識する受容体の1つであるToll like receptor 2を介した刺激により抑制されることを示した。これらは、腸管の恒常性の破綻を食品成分により抑制するための標的として有用である。

Research Products

• [Journal Article] Intestinal Bifidobacteriumassociation in germ-free T cell receptor transgenic mice down-regulates dietary antigen-specific immune responses of the small intestine but enhances those of the large intestine (2009)
  • Author(s): Tsuda M, Hosono A, YanagibashiT, Hachimura S, Hirayama K, Umesaki Y, Itoh K, Takahashi K, and Kaminogawa S
  • Journal Title: Immunobiology 214 Pages: 279-289
  • Peer Reviewed
• [Journal Article] Bacteroides induce higher IgA production than Lactobacillus by increasing activation-induced cytidine deaminase expression on B cells in murine Peyer's patches (2009)
  • Author(s): Yanagibasi T, Hosono A, Oyama A, Tsuda M, Hachimura S, Takahashi Y, Itoh K, Hirayama K, Takahashi K, and KaminogawaS
  • Journal Title: Biosci. Biotechnol. Biochem 73 Pages: 372-377
  • NAID: 10027537465
  • Peer Reviewed
• [Journal Article] A TLR2 ligand suppresses allergic inflammatory reactions by acting directly on mast cells (2009)
  • Author(s): Kasakura K, Takahashi K, Aizawa T, Hosono A, and Kaminogawa S
  • Journal Title: Int. Arch. Allergy Immunol (In press)
  • Peer Reviewed
• [Journal Article] Intestinal Bifidobacterium association in germ-free T cell receptor transgenic mice down-regulates dietary antigen-specific immune responses of the small intestine but enhances those of the large intestine (2009)
  • Author(s): Tsuda M, Hosono A, Yanagibashi T, Hachimura S, Hirayama K, Umesaki Y, Itoh K, Takahashi K, and Kaminogawa S
  • Journal Title: Inimunobiology 214 Pages: 279-289
  • Peer Reviewed
• [Journal Article] Bacteroides induce higher IgA production than Lactobacillus by increasing activation-induced cytidine deaminase expression on B cells in murine Peyer's natches (2009)
  • Author(s): Yanagibasi T, Hosono A, Oyama A, Tsuda M, Hachimura S, Takahashi Y, Itoh K, Hirayama K, Takahashi K, and KaminogawaS
  • Journal Title: Biosci. Biotechnol. Biochem 73 Pages: 372-377
  • Peer Reviewed
• [Journal Article] Cooperative regulation of FcRγ gene expression by multiple transcription factors including Sp1 (2008)
  • Author(s): Takahashi K, Hayashi N, ShimokawaT, Umehara N, Kaminogawa S, and Ra C
  • Journal Title: GABP and Elf-1 J. Biol. Chem 283 Pages: 15134-15141
  • Peer Reviewed
• [Journal Article] Cooperative regulation of FcRγ gene expression by multiple transcription factors including Spl, GABP and Elf-1 (2008)
  • Author(s): Takahashi K, Hayashi N, ShimokawaT, Umehara N, Kaminogawa S, and Ra C.
  • Journal Title: J. Biol. Chem. (in press)
  • Peer Reviewed
• [Journal Article] Bifidobacterium components have immunomodulatory characteristics dependant on the method of preparation (2007)
  • Author(s): Hiramatsu Y, Hosono A, Takahashi K, andKaminogawa S
  • Journal Title: Cytotechnology 55 Pages: 79-87
  • Peer Reviewed
• [Journal Article] Prior stimulation of antigen-presenting cells with Lactobacillus regulates excessive antigen-specific cytokine responses in vitro when compared with Bacteroides (2007)
  • Author(s): Tsuda M, Hosono A, Yanagibashi T, Hachimura S, Hirayama K, Itoh K, Takahashi K, and Kaminogawa S
  • Journal Title: 55 Pages: 89-101
  • Peer Reviewed
• [Journal Article] Bifidobacterium components have immunomodulatory characteristics dependant on the method of prepazation. (2007)
  • Author(s): Hiramatsu Y, Hosono A, Takahashi K, and Kaminogawa S.
  • Journal Title: Cytotechnology 55 Pages: 79-87
  • Peer Reviewed
• [Journal Article] Prior stimulation of antigen-presenting cells with Lactobacillus regulates excessive antigen-specific cytokine responses in vitro when compared with Bacteroides. (2007)
  • Author(s): Tsuda M, Hosono A, Yanagibashi T, Hachimura S, Hirayama K, Itoh K, Takahashi K, and Kaminogawa S.
  • Journal Title: Cytotechnology 55 Pages: 89-101
  • Peer Reviewed
• [Journal Article] A TLR2 ligand suppresses allergic inflammatory reactions by acting directly on mast cells
  • Author(s): Kasakura K, Takahashi K, Aizawa T, Hosono A, and Kaminogawa S
  • Journal Title: Int. Arch. Allergy Immunol (in press)
  • Peer Reviewed
• [Presentation] マスト細胞のアレルギー応答のTLR2依存的な抑制 (2009)
  • Author(s): 笠倉和巳、高橋恭子、細野朗、上野川修一
  • 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] 腸管上皮細胞におけるTollip遺伝子の発現制御機構 (2009)
  • Author(s): 杉由高、高橋恭子、細野朗、上野川修一
  • 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] 腸内細菌がマスト細胞の最終分化に及ぼす影響 (2009)
  • Author(s): 國井潤一、高橋恭子、笠倉和巳、細野朗、上野川修一
  • Organizer: 日本農芸化学会2009年度大会2008年12月3日国立京都国際会館
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-29
• [Presentation] マスト細胞のアレルギー応答のTLR2依存的な抑制 (2009)
  • Author(s): 笠倉和巳、高橋恭子、細野朗、上野川修一
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2009-03-29
• [Presentation] 腸管上皮細胞におけるTollip遺伝子の発現制御機構 (2009)
  • Author(s): 杉由高、高橋恭子、細野朗、上野川修一
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2009-03-29
• [Presentation] 腸内細菌がマスト細胞の最終分化に及ぼす影響 (2009)
  • Author(s): 國井潤一、高橋恭子、笠倉和巳、細野朗、上野川修一
  • Organizer: 日本農芸化学会2009年度大会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2009-03-29
• [Presentation] Suppressive effects of TLR2 ligands on allergic reactions of mast cells (2008)
  • Author(s): Kasakura K, Takahashi K, Hosono A, Kaminogawa S
  • Organizer: 日本免疫学会第38回学術集会2008年12月3日国立京都国際会館
  • Place of Presentation: 京都
  • Year and Date: 2008-12-03
• [Presentation] Suppressive effects of TLR2 ligands on allergic reactions of mast cells (2008)
  • Author(s): Kasakura K, Takahashi K, Hosono A, Kaminogawa S
  • Organizer: 日本免疫学会第38回学術集会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2008-12-03
• [Presentation] Regulatory mechanisms of TLR4 gene transcription in intestinal epithelial cells (2008)
  • Author(s): Takahashi K, Sugi Y, Hosono A, and Kaminogawa S
  • Organizer: 日本免疫学会第38回学術集会2008年12月3日国立京都国際会館
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] IEC-specific regulation of Tollip gene expression (2008)
  • Author(s): Sugi Y, Takahashi K, Hosono A, and Kaminogawa S
  • Organizer: 日本免疫学会第38回学術集会2008年12月3日国立京都国際会館
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] Regulatory mechanisms of TLR4 gene transcription in intestinal epithel ial cells (2008)
  • Author(s): Takahashi K, Sugi Y, Hosono A. and Kaminogawa S
  • Organizer: 日本免疫学会第38回学術集会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2008-12-02
• [Presentation] IEC-specific regulation of Tollip gene expression (2008)
  • Author(s): Sugi Y, Takahashi K, Hosono A, and Kaminogawa S
  • Organizer: 日本免疫学会第38回学術集会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2008-12-02
• [Presentation] 腸管上皮細胞におけるTollip遺伝子の発現制御機構 (2008)
  • Author(s): 杉由高、高橋恭子、細野朗、上野川修一
  • Organizer: 第11回腸内細菌学会
  • Place of Presentation: 東京大学弥生講堂(東京)
  • Year and Date: 2008-06-12
• [Presentation] TLR2リガンドによるマスト細胞のアレルギー応答の抑制 (2008)
  • Author(s): 笠倉和巳、高橋恭子、細野朗、上野川修一
  • Organizer: 日本食品免疫学会2008年度大会
  • Place of Presentation: 駒場エミナース(東京)
  • Year and Date: 2008-05-13
• [Presentation] 腸管上皮細胞におけるTollip遺伝子の発現制御機構 (2008)
  • Author(s): 杉由高、高橋恭子、細野朗、上野川修一
  • Organizer: 日本農芸化学会2008年度大会
  • Place of Presentation: 名城大学天白キャンパス(名古屋)
  • Year and Date: 2008-03-28
• [Presentation] TLR2を介したマスト細胞のアレルギー応答の抑制とその機序 (2008)
  • Author(s): 笠倉和巳、高橋恭子、細野朗、上野川修一
  • Organizer: 日本農芸化学会2008年度大会
  • Year and Date: 2008-03-28
• [Presentation] 腸内細菌は小腸におけるIgA産生より大腸におけるそれに強く影響する (2008)
  • Author(s): 柳橋努、細野朗、津田真人、八村敏志、高橋宜聖、平山和弘、伊藤喜久治、高橋恭子、上野川修一
  • Organizer: 日本農芸化学会2008年度大会
  • Place of Presentation: 名城大学天白キャンパス(名古屋)
  • Year and Date: 2008-03-28
• [Presentation] 腸内細菌はパイエル板細胞の経口抗原に対するサイトカイン産生の抑制と制御性T細胞の発現を誘導する (2008)
  • Author(s): 津田真人、細野朗、柳橋努、八村敏志、平山和弘、伊藤喜久治、高橋恭子、上野川修一
  • Organizer: 日本農芸化学会2008年度大会
  • Place of Presentation: 名城大学天白キャンパス(名古屋)
  • Year and Date: 2008-03-28
• [Presentation] Regulation of TLR gene expression in intestinal epithelial cells (2007)
  • Author(s): Takahashi K, Hosono A, Kaminogawa S
  • Organizer: 日本免疫学会第37回学術集会
  • Place of Presentation: グランドプリンスホテル新高輪(東京)
  • Year and Date: 2007-11-21
• [Presentation] Direct effects of Lactobacillus GG and L. gasseri TMC0356 on mast cells. (2007)
  • Author(s): Harata G, Takahashi K, He F, Kubota A, Hosono A, Kaminogawa S
  • Organizer: 日本免疫学会第37回学術集会
  • Place of Presentation: グランドプリンスホテル新高輪(東京)
  • Year and Date: 2007-11-21
• [Presentation] Direct effects of Lactobacillus GG and L. gasseri TMCO356 on mast cells (2007)
  • Author(s): Harata G, Takahashi K, He F, Kubota A, Hosono A, Kaminogawa S.
  • Organizer: 日本免疫学会第37回学術集会
  • Place of Presentation: グランドプリンスホテル新高輪(東京)
  • Year and Date: 2007-11-21
• [Presentation] Differentiated implication of Lactobacillus GG and L. gasseri TMC0356 on gut-associated immune lymphoid tissues (2007)
  • Author(s): Harata G, He F, Kawase M, Kubota A, Hiramatsu M, Hosono A, Takahashi K, Kaminogawa S
  • Organizer: The 4th Asian Conference on Lactic Acid Bacteria
  • Place of Presentation: Shanghai Everbright Convention & Exhibition Centre International Hotel (China)
  • Year and Date: 2007-10-14
• [Presentation] Differentiated implication of Lactobacillus GG and L. gasseri TMC0356 on gut-associated immune lymphoid tissues (2007)
  • Author(s): Harata C, He F, Kawase M, Kubota A, Hiramatsu M, Hosono A, Takahashi K, Kaminogawa S.
  • Organizer: The 4th Asian Conference on Lactic Acid Bacteria
  • Place of Presentation: Shanghai Everbright Contention & Exhibition Centre International Hotel (China)
  • Year and Date: 2007-10-14
• [Presentation] Murine intestinal commensal Lactobacillus modulates antigen-specific cytokine production via antigen-presenting cells differently to Bacteroides (2007)
  • Author(s): Tsuda M, Hosono A, Yanagibashi T, Hachimura S, Hirayama K, Itoh K, Takahashi K, Kaminogawa S
  • Organizer: Murine intestinal commensal Lactobacillus modulates antigen-specific cytokine production via antigen-presenting cells differently to Bacteroides
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2007-07-11
• [Presentation] Bacteroides acidofaciens induces differentiation of IgM+ cells into IgA-plasma cells from the large intestine (2007)
  • Author(s): Yanagibashi T, Hosono A, Tsuda M, Hachimura S, Takahashi Y, Hirayama K, Itoh K, Takahashi K, Kaminogawa S
  • Organizer: 13th International Congress of Mucosal Immnuology
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2007-07-11
• [Presentation] Murine intestinal commensal Lactobacillus modulates antigen-specific cytokine production via antigen-presenting cells differently to Bacteroides (2007)
  • Author(s): Tsuda M, Hosono A, Yanagibashi T, Hachimura S, Hirayama K, Itoh K, Takahashi K, Kaminogawa S.
  • Organizer: 13th International Congress of Mucosal Immnuology
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2007-07-11
• [Presentation] Bacteroides acidofaciens induces differentiation of IgM+cells into IgA-plasma cells from the large intestine (2007)
  • Author(s): Yanagibashi T, Hosono A, Tsuda M, Hachimura S, Takahashi Y, Hirayama K, Itoh K, Takahashi K, Kaminogawa S.
  • Organizer: 13th International Congress of Mucosal Immnuology
  • Place of Presentation: 品川プリンスホテル(東京)
  • Year and Date: 2007-07-11
• [Presentation] 腸内細菌由来菌体成分によるマスト細胞のアレルギー応答の調節 (2007)
  • Author(s): 相澤奉文、高橋恭子、笠倉和己、細野朗、上野川修一
  • Organizer: 日本動物細胞工学会2007年度大会
  • Place of Presentation: 高崎シティギャラリー(高崎)
  • Year and Date: 2007-07-04
• [Presentation] 処理条件の異なるBifidobacterium菌体調製物とその免疫修飾作用の相関について (2007)
  • Author(s): 平松靖浩、細野朗、高橋恭子、上野川修一
  • Organizer: 日本動物細胞工学会2007年度大会
  • Place of Presentation: 高崎シティギャラリー(高崎)
  • Year and Date: 2007-07-04
• [Presentation] 調製法の異なるBifidobacterium菌体成分が修飾する免疫応答の特徴 (2007)
  • Author(s): 平松靖浩、細野朗、高橋恭子、上野川修一
  • Organizer: 第11回腸内細菌学会
  • Place of Presentation: 北里大学薬学部(東京)
  • Year and Date: 2007-06-14