Basic studies on the prevention and improvement on intestinal bowel disease by immunobiotics and their advanced application

• Project/Area Number: 18380158
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Zootechnical science/Grassland science
• Research Institution: Tohoku University
• Principal Investigator: KITAZAWA Haruki Tohoku University, 大学院・農学研究科, 准教授 (10204885)
• Co-Investigator(Kenkyū-buntansha): SAITO Tadao 東北大学, 大学院・農学研究科, 教授 (00118358) ; ASO Hisashi 東北大学, 大学院・農学研究科, 准教授 (50241625) ; KAWAI Yasushi 東北大学, 大学院・農学研究科, 助教 (00261496)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,010,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,610,000); Fiscal Year 2008: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2006: ¥6,700,000 (Direct Cost: ¥6,700,000)
• Keywords: プロバイオティクス / イムノバイオティクス / 乳酸菌 / 炎症性腸疾患 / 抗炎症性 / パタ-ン認識受容体 / ブタ / パターン認識受容体 / IBD / Nod / TLR

Research Abstract

本研究は、炎症性腸疾患の予防に有効な、新規「イムノバイオティック食品」の開発基盤を築くことを目的とし、ヒトモデルとして期待されるブタ腸管上皮細胞株(PIE細胞)を用いて、イムノバイオティクスの抗炎症活性について解析した。その結果、パタ-ン認識受容体を介して抗炎症性を発揮するイムノバイオティクスの選抜が可能となり、その機構解明が飛躍的に進むことが大いに期待され、「イムノバイオティック食品」の創製に向けた開発基礎が得られた。

Research Products

• [Journal Article] Utilization of the porcine system to study lymphotoxin-β regulation in intestinal lymphoid tissue (2009)
  • Author(s): Shimazu, T., M. Tohno, S. Katoh, T. Shimosato, H. Aso, Y. Kawai, T. Saito, H. Kitazawa
  • Journal Title: Biochem.Genet 47 Pages: 126-136
  • Peer Reviewed
• [Journal Article] ヒトモデルとしてのブタにおけるTLRファミリ-の解析と乳業界における発展的利用性 (2009)
  • Author(s): 遠野雅徳、齋藤忠夫、北澤春樹
  • Journal Title: ミルクサイエンス 57 Pages: 79-85
  • NAID: 130003398668
  • Peer Reviewed
• [Journal Article] Utilization of the porcine system to study lymphotoxin-βregulation in intestinal lymphoid tissue (2009)
  • Author(s): Shimazu, T., Kitazawa, H., et.al.
  • Journal Title: Biochem. Genet. 47 Pages: 126-136
  • Peer Reviewed
• [Journal Article] Physiol-Gastrointest (2008)
  • Author(s): Kanaya, T., K. Miyazawa, I. Takakura, W. Itani, K. Watanabe, S. Ohwada, H. Kitazawa, M. T. Rose, H. R. McConochie, H. Okano, T. Yamaguchi, H. Aso. Am. J
  • Journal Title: Liver Phys 295
  • Peer Reviewed
• [Journal Article] Molecular cloning and functional characterization of porcine nucleotide- binding oligomerization domain-1 (NOD1) recognizing minimum agonists (2008)
  • Author(s): Tohno, M., T. Shimazu, H. Aso, A. Uehara, H. Takada, A. Kawasaki, Y. Fujimoto, K. Fukase, T. Saito, H. Kitazawa
  • Journal Title: meso- diaminopimelic acid and meso-lanthionine. Mol. Immunol 45 Pages: 1807-1817
  • Peer Reviewed
• [Journal Article] Immunostimulatory oligo- deoxynucleotide containing TTTCGTTT motif from Lactobacillus rhamnosus GG DNA potentially suppresses OVAspecific IgE production in mice (2008)
  • Author(s): Iliev, I.D., M. Tohno, D. Kurosaki, T. Shimosato, F. He, M. Hosoda, T. Saito, H. Kitazawa
  • Journal Title: Scand. J. Immunol 67 Pages: 370-376
  • Peer Reviewed
• [Journal Article] Toll-like receptor 4 and cytokine expression involved in functional immune response in an originally established porcine intestinal epitheliocyte cell line (2008)
  • Author(s): Moue, M., M. Tohno, T. Shimazu, T. Kido, H. Aso, T. Saito, H. Kitazawa
  • Journal Title: BBA-Gen. Subjects 1780 Pages: 134-144
  • Peer Reviewed
• [Journal Article] Molecular cloning and functional characterization of porcine Nucleotide- binding oligomerization domain-2 (NOD2) (2008)
  • Author(s): Tohno, M., W. Ueda, Y. Azuma, T. Shimazu, S. Katoh, J.M. Wang, H. Aso, H. Takada, Y. Kawai, T. Saito, H. Kitazawa
  • Journal Title: Mol. Immunol 45 Pages: 194-203
  • Peer Reviewed
• [Journal Article] Development of molecular immuno- assay system for probiotics via Toll-like receptors based on food immunology (2008)
  • Author(s): Kitazawa, H., M. Tohno, T. Shimosato, T. Saito
  • Journal Title: Anim. Sci. J 79 Pages: 11-21
  • NAID: 10025368422
  • Peer Reviewed
• [Journal Article] Immunostimulatory oligodeoxynucleotide containing TTTCGTTT motif from Lactobacillus rhamnosus GG DNA potentially suppresses OVAspecific IgE production in mice (2008)
  • Author(s): Iliev, I. D., Kitazawa, H., et.al.
  • Journal Title: Scand. J. Immunol. 67 Pages: 370-376
  • Peer Reviewed
• [Journal Article] Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-1 (NOD1) recognizing minimum agonists, meso-diaminopimelic acid and meso-lanthionine (2008)
  • Author(s): Tohno. M.. Kitazawa. H., et.al.
  • Journal Title: Mol. Immunol. 45 Pages: 1807-1817
  • Peer Reviewed
• [Journal Article] Differentiation of a murine intestinal epithelial cell line (MIE) towards the M cell lineage (2008)
  • Author(s): Kanaya, T., Kitazawa, H.,Aso, H., et.al.
  • Journal Title: J. Physiol-Gastrointest. Liver Phys. 295
  • Peer Reviewed
• [Journal Article] プロバイオテイクスからイムノバイオテイクス〜生体認識機構の解明から期待される世界的発展性〜 (2008)
  • Author(s): 北澤春樹、遠野雅徳
  • Journal Title: 「世界の発酵乳」(はる書房) Pages: 152-171
  • Peer Reviewed
• [Journal Article] ヒトモデルとしてのブタにおけるTLRファミリーの解析と乳業界における発展的利用性 (2008)
  • Author(s): 遠野雅徳、齋藤忠夫、北澤春樹
  • Journal Title: ミルクサイエンス 59 Pages: 79-85
  • NAID: 130003398668
  • Peer Reviewed
• [Journal Article] Toll-like receptor 4 and cytokine expression involved in functional immune response in an originally established porcine intestinal epitheliocyte cell line. (2008)
  • Author(s): Moue, M., Kitazawa, H., et. al.
  • Journal Title: BBA-Gen. Subjects 1780 Pages: 134-144
  • Peer Reviewed
• [Journal Article] Development of molecular immunoassay system for probiotics via Toll-like receptors based on food immunology. (2008)
  • Author(s): Kitazawa, H., et. al.
  • Journal Title: Anim. Sci. J. 79 Pages: 11-21
  • NAID: 10025368422
  • Peer Reviewed
• [Journal Article] Molecular cloning and functional characterization of porcine Nucleotide-binding oligomerization domain-2 (NOD2). (2008)
  • Author(s): Tohno, M., Kitazawa, H., et. al.
  • Journal Title: Mol. Immunol 45 Pages: 194-203
  • Peer Reviewed
• [Journal Article] Molecular cloning and functional characterization of porcine MyD88 essential for TLR signaling (2007)
  • Author(s): Tohno, M., T. Shimazu, H. Aso, Y. Kawai, T. Saito, H. Kitazawa
  • Journal Title: Cell. Mol. Immunol 4 Pages: 369-376
  • Peer Reviewed
• [Journal Article] An advanced molecular immunoassay system for immunobiotic lactic acid bacteria using a transfectant of Toll-like receptor 2 (2007)
  • Author(s): Tohno, M., T. Shimosato, Y. Kawai, H. Aso, S. Ikegami, N. Taketomo, T. Saito, H.Kitazawa
  • Journal Title: Anim. Sci. J 78 Pages: 195-205
  • NAID: 10021224817
  • Peer Reviewed
• [Journal Article] Molecular cloning of porcine RP105/MD-1 involved in recognition of extracellular phosphopolysaccharides from Lactococcus lactis ssp. Cremoris (2007)
  • Author(s): Tohno, M., T. Shimazu, W. Ueda, D. Anzawa, H. Aso, J. Nishimura, Y. Kawai, Y. Saito, T. Saito, H. Kitazawa
  • Journal Title: Mol. Immunol 44 Pages: 2566-2577
  • Peer Reviewed
• [Journal Article] Molecular cloning and functional characterization of porcine MyD88 essential for TLR signaling. (2007)
  • Author(s): Tohno, M., Kitazawa, H., et. al.
  • Journal Title: Cell. Mol. Immunol. 4 Pages: 369-376
  • Peer Reviewed
• [Journal Article] Enzymatic digestion of the milk protein<beta>-casein releases potent chemotactic peptide(s) for monocytes and macrophages. (2007)
  • Author(s): Kitazawa, H., et. al.
  • Journal Title: Int. Immunopharmacol. 7 Pages: 1150-1159
  • Peer Reviewed
• [Journal Article] Molecular cloning of porcine PR105/MD-1 involved in recongnition of extreacellular phosphopolysaccharides from Lactococcus lactis ssp. cremoris. (2007)
  • Author(s): Tohno, M., Kitazawa, H., et al.
  • Journal Title: Mol. Immunol. 44 Pages: 2566-2577
• [Journal Article] An advanced molecular immunoassay system for immunobiotic lactic acid bacteria using a transfectant of Toll-like receptor 2. (2007)
  • Author(s): Tohno, M., Kitazawa, H., et al.
  • Journal Title: Anim. Sci. J. 78 Pages: 195-205
  • NAID: 10021224817
• [Journal Article] Toll-like receptor 2 and 9 are expressed and functional in gut-associated lymphoid tissues of presuckling newborn swine (2006)
  • Author(s): Tohno, M., T. Shimosato, M. Mouea, H. Aso, K. Watanabe, Y. Kawai, T. Yamaguchi, T. Saito, H. Kitazawa
  • Journal Title: Vet. Res 37 Pages: 791-812
  • Peer Reviewed
• [Journal Article] 豚腸管におけるToll様受容体の機能発現と食品免疫学への応用 (2006)
  • Author(s): 北澤春樹、遠野雅徳、下里剛士、齋藤忠夫
  • Journal Title: 獣医畜産新報 59 Pages: 559-561
  • Peer Reviewed
• [Journal Article] Toll-like receptor 2 and 9 are expressed and functional ingut-associated lymphoid tissues of presuckling newbron swine. (2006)
  • Author(s): Tohno, M., Kitazawa, H., et al.
  • Journal Title: Vet. Res. 37 Pages: 791-812
• [Journal Article] Swine intestinal immunity via Toll-like Receptors and its advanced application to food immunology. (2006)
  • Author(s): Kitazawa, H., et al.
  • Journal Title: J. Integ. Field Sci. 3 Pages: 9-14
• [Journal Article] 豚腸管におけるToll様受容体の機能発現と食品免疫学への応用. (2006)
  • Author(s): 北澤春樹, 他
  • Journal Title: 獣医畜産新報 59 Pages: 559-561
• [Presentation] イムノバイオティクスのブタ腸管上皮細胞における抗炎症作用 (2009)
  • Author(s): 島津朋之、遠野雅徳、下里剛士、麻生久、川井泰、齋藤忠夫、北澤春樹
  • Organizer: 日本畜産学会第110回大会
  • Place of Presentation: 日本大学、藤沢市
• [Presentation] Streptococcus thermophilus lacZからの強免疫刺激性DNAモチーフの発見 (2009)
  • Author(s): 下里剛士、遠野雅徳、西村順子、川井泰、齋藤忠夫、北澤春樹
  • Organizer: 日本畜産学会第110回大会
  • Place of Presentation: 日本大学、藤沢市
• [Presentation] Development of evaluation system for immunobiotics, Multilateral Workshop (2008)
  • Author(s): Kitazawa, H., H. Aso
  • Organizer: Challenge for the reduction of antimicrobial use in animal production
  • Place of Presentation: つくば国際会議場、 つくば
  • Year and Date: 2008-11-11
• [Presentation] Development of evaluation system for immunobiotics (2008)
  • Author(s): Kitazawa, H., Aso, H.
  • Organizer: Multilateral Workshop, "Challenge for the reduction of antimicrobial use in animal production."
  • Place of Presentation: つくば国際会議場、つくば
  • Year and Date: 2008-11-11
• [Presentation] An immuno- evaluation system for anti-inflammatory probiotics using originally established porcine epitheliocyte(PIE) cells (2008)
  • Author(s): Shimazu, T., M. Tohno, M. Moue, H. Aso, T. Saito, H. Kitazawa
  • Organizer: ADSA-ASAS Joint Meeting
  • Place of Presentation: Indianapolis, USA
• [Presentation] Immuno-stimulatory AT oligo- deoxynucleotide from Lactobacillus gasseri requires a specific self- stabilized structure (2008)
  • Author(s): Shimosato, T., M. Tohno, T. Sato, Y. Kawai, T. Saito, H. Kitazawa
  • Organizer: ADSA-ASAS Joint Meeting
  • Place of Presentation: Indianapolis, USA
• [Presentation] ブタ腸管上皮細胞によるプロバイオティクスの新規ヒトモデル腸管抗炎症評価系の構築 (2008)
  • Author(s): 島津朋之、遠野雅徳、馬上真之、藤江瞳、川井泰、麻生久、齋藤忠夫、北澤春樹
  • Organizer: 日本畜産学会第109回大会
  • Place of Presentation: 水戸市
• [Presentation] 新規ブタ腸管上皮細胞株を用いた抗炎症性プロバイオティクスの分子免疫評価系構築 (2008)
  • Author(s): 島津朋之、北澤春樹, ら
  • Organizer: 日本食品免疫学会第4回学術大会
  • Place of Presentation: こまばエミナース、東京
• [Presentation] プロバイオティック乳酸菌由来ATオリゴヌクレオチドの2次構造特性とTLR9結合領域の解明 (2008)
  • Author(s): 下里剛士、北澤春樹, ら
  • Organizer: 日本食品免疫学会第4回学術大会
  • Place of Presentation: こまばエミナース、東京
• [Presentation] An immuno-evaluation system for and-inflammatory probiotics usin goriginally established porcine epitheliocyte (PIE) cells (2008)
  • Author(s): Shimazu, T., Kitazawa, H., et.al.
  • Organizer: ADSA-ASAS Joint Meeting
  • Place of Presentation: Indianapolis, USA
• [Presentation] Immuno-stimulatory AT oligodeoxynucleotide from Lactobacill us gasseri requires a specific self-stabilized structure (2008)
  • Author(s): Shimosato, T., Kitazawa, H., et.al.
  • Organizer: ADSA-ASAS Joint Meeting
  • Place of Presentation: Indianapolis, USA
• [Presentation] Preferential expression of lymphotoxin-β by immunobiotics in GALTs of neonatal swine (2007)
  • Author(s): Shimazu, T., M. Tohno, S. Katoh, T. Shimosato, H. Aso, Y. Kawai, T. Saito, H. Kitazawa
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: Shinagawa, Tokyo
  • Year and Date: 2007-10-11
• [Presentation] Extra- cellular phosphopolysaccharides from Lactococcus lactis ssp. cremoris is a novel ligand for porcine RP105/MD-1 strongly expressed in gut-associated lymphoid tissues (2007)
  • Author(s): Tohno, M., T. Shimazu, W. Ueda, D. Anzawa, H. Aso, J. Nishimura, Y. Kawai, Y. Saito, T. Saito, H. Kitazawa
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: Tokyo
  • Year and Date: 2007-10-11
• [Presentation] ブタ腸管におけるNOD1および2の発現とイムノバイオティクスによる発現増強 (2007)
  • Author(s): 遠野雅徳、植田 渉、島津朋之、森江恭子、麻生久、川井泰、齋藤忠夫、北澤春樹
  • Organizer: 日本畜産学会第108回大会
  • Place of Presentation: 岡山市
• [Presentation] Immunoregulatory Factors from Probiotics.(invited) (2007)
  • Author(s): Kitazawa, H., M. Tohno, T. Saito
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: Shinagawa, Tokyo
• [Presentation] ブタ腸管におけるイムノバイオティクスのTLR2を介する免疫機能発現 (2007)
  • Author(s): 遠野雅徳、島津朋之、川井泰、齋藤忠夫、麻生久、北澤春樹
  • Organizer: 日本畜産学会第107回大会
  • Place of Presentation: 相模原市
• [Presentation] ブタlymphotoxin-β(LT-β)のクロ-ニングと腸管における発現増強 (2007)
  • Author(s): 島津朋之、遠野雅徳、加藤真一郎、下里剛士、麻生久、 川井泰、 齋藤忠夫、 北澤春樹
  • Organizer: 日本畜産学会第107回大会
  • Place of Presentation: 相模原市
• [Presentation] Immunoregulatory factors from probiotics. (2007)
  • Author(s): Kitazawa, H., et. al.
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: Tokyo
• [Presentation] Extracellular phosphopolysaccharides from Lactococcus lactis ssp. cremoris is a novel ligand for porcine RP105/MD-1 strongly expressed in gut-associated lymphoid tissues. (2007)
  • Author(s): Tohno, M., Kitazawa, H., et. al.
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: Tokyo
• [Presentation] Preferential expression of lymphotoxin-b by immunobiotics in GALTs of neonatal swine. (2007)
  • Author(s): Shimazu, T., Kitazawa, H., et. al.
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: Tokyo
• [Presentation] Immunomodulatory effects of extracellular phosphopolysaccharide from Lactococcus lactis ssp. cremoris GCL1176 in a murine model of allergic inflammation. (2007)
  • Author(s): Anzawa, D., Kitazawa, H., et. al.
  • Organizer: The 4th Asian Conference on Lactic Acid Bacteria
  • Place of Presentation: Shanghai, China
• [Presentation] ブタ腸管におけるNOD1および2の発現とイムノバイオティクスによる発現増強. (2007)
  • Author(s): 遠野, 北澤, ら
  • Organizer: 日本畜産学会第108回大会
  • Place of Presentation: 岡山
• [Presentation] ブタPGLYRPおよび4のクローニングと腸管における発現増強. (2007)
  • Author(s): 植田, 北澤, ら
  • Organizer: 日本畜産学会第108回大会
  • Place of Presentation: 岡山
• [Presentation] イムノバイオティクスが有する免疫スペクトルの比較解析. (2007)
  • Author(s): 森江, 北澤, ら
  • Organizer: 日本畜産学会第108回大会
  • Place of Presentation: 岡山
• [Presentation] βカゼインの酵素消化によるモノサイト/マクロファージ走化性ペプチドの生成. (2007)
  • Author(s): 北澤, ら
  • Organizer: 日本畜産学会第108回大会
  • Place of Presentation: 岡山
• [Presentation] TLRの腸管における機能発現を基礎としたイムノバイオティック評価系の構築 (2006)
  • Author(s): 遠野雅徳、北澤春樹
  • Organizer: 日本食品免疫学会, 第2回学術大会シンポジウム1
  • Place of Presentation: 昭和女子大学、東京
• [Presentation] プロバイオティクスの細胞内レセプターNodを介する分子免疫活性評価系の構築 (2006)
  • Author(s): 四阿祐子、遠野雅徳、下里剛士、加藤真一郎、川井泰、齋藤忠夫、北澤春樹
  • Organizer: 第56回東北畜産学会大会
  • Place of Presentation: 秋田市
• [Presentation] Development of a novel immunoassay system for immunobiotics that madulate intestinal immunity through Toll-like receptor 2 (2006)
  • Author(s): Tohno, M., T. Shimosato, Y. Kawai, T. Saito, H. Kitazawa
  • Organizer: ADSA-ASAS Joint Meeting
  • Place of Presentation: Minneapolis, USA
• [Presentation] Immunobiotic lactic acid bacteria induce immune responses in immature gut-associated lymphoid tissues via Toll-like receptors 2 and 9 (2006)
  • Author(s): Kitazawa, H., M. Tohno, T. Shimosato, H. Aso, Y. Kawai, T. Saito
  • Organizer: ADSA-ASAS Joint Meeting
  • Place of Presentation: Minneapolis, USA
• [Book] プロバイオティクスからイムノバイオティクス~生体認識機構の解明から期待される世界的発展性~、「世界の発酵乳」分担 (2008)
  • Author(s): 北澤春樹、遠野雅徳
  • Publisher: はる書房
• [Patent(Industrial Property Rights)] Drug and food composition for enhancing immune responce conaining AT oligonucleotide as the active ingredient (2006)
  • Inventor(s): Kitazawa, H, T. Saito, T. Shimosato, T. Sasaki, Y. Ito
  • Industrial Property Rights Holder: 明治ホ-ルディングス(株)
  • Filing Date: 2006-09-08
  • Overseas