Molecular immunoregulations in the intestinal inflammatory cell intranet by immunobiotics for their advanced application

• Project/Area Number: 24380146
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Zootechnical science/Grassland science
• Research Institution: Tohoku University
• Principal Investigator: Kitazawa Haruki 東北大学, (連合)農学研究科(研究院), 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, 教授 (50241625) ; 川井 泰 東北大学, 大学院・農学研究科, 助教 (00261496)
• Co-Investigator(Renkei-kenkyūsha): SUDA YOSHIHITO 宮城大学, 食産業学部, 教授 (90404847)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 畜産学 / 免疫学 / プロバイオティクス / イムノバオティクス / 微生物 / 食品 / 飼料 / 動物 / イムノバイオティクス

Outline of Final Research Achievements

In this study, detailed mechanisms for the recognition and anti-inflammation of immunobiotics in the gut was analyzed by using livestock intestinal epithelial and dendritic cells. As a result, high recognition for immunobiotics by porcine dendritic cells was observed and a common intracellular regulator induced by immunobiotics was found in porcine intestinal epitheliocytes. Furthermore, anti-inflammatory ability of immunobiotics could be verified in vivo study. This study contributes to progress an understanding the molecular regulation of inflammatory cell intranet by immunobiotics.

Research Products

• [Int'l Joint Research] CERELA-CONICET(アルゼンチン)
• [Journal Article] 2.Immunobiotic Bifidobacteria Strains Modulate Rotavirus Immune Response in Porcine Intestinal Epitheliocytes via Pattern Recognition Receptor Signaling. (2016)
  • Author(s): Ishizuka T, Kanmani P, Kobayashi H, Miyazaki A, Soma J, Suda Y, Aso H, Nochi T, Iwabuchi N, Xiao JZ, Saito T, Villena J, Kitazawa H.
  • Journal Title: PLoS One. Volume: 11 Issue: 3 Pages: 1-19
  • DOI: 10.1371/journal.pone.0152416
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Draft Genome Sequence of Lactobacillus plantarum CRL1506, an immunomodulatory strain isolated from goat milk. (2016)
  • Author(s): Saavedra, L., H. Kitazawa, J. Villena et al.
  • Journal Title: Genome Announc. Volume: 4(2):e00108-16 Issue: 2 Pages: 1-2
  • DOI: 10.1128/genomea.00108-16
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The toll-like receptor family protein RP105/MD-1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14. (2015)
  • Author(s): Murofushi, Y., J. Villena, P. Kanmani, H. Kitazawa et al.
  • Journal Title: Mol. Immunol. Volume: 64 Issue: 1 Pages: 63-75
  • DOI: 10.1016/j.molimm.2014.10.027
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lactobacillus delbrueckii TUA4408L and its extracellular polysaccharides attenuate Enterotoxigenic Escherichia coli induced inflammatory response in porcine intestinal epitheliocytes via Toll-like receptor-2 and 4. (2014)
  • Author(s): Wachi, S., P. Kanmani, H. Kitazawa et al.
  • Journal Title: Mol. Nutr. Food Res. Volume: 58 Issue: 10 Pages: 2080-2093
  • DOI: 10.1002/mnfr.201400218
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of Toll-like receptors-mediated inflammation by immunobiotics in bovine intestinal epitheliocytes: role of signalling pathways and negative regulators. (2014)
  • Author(s): Villena, J., H. Aso, H. Kitazawa
  • Journal Title: Front. Immunol. Volume: 5(421) Pages: 1-10
  • DOI: 10.3389/fimmu.2014.00421
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve growth performance and productivity in post-weaning pigs. (2014)
  • Author(s): Suda, Y., H. Aso, H. Kitazawa et al.
  • Journal Title: BMC Immunol. Volume: 15(24) Issue: 1 Pages: 1-18
  • DOI: 10.1186/1471-2172-15-24
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunobiotic Lactobacillus rhamnosus strains differentially modulate antiviral immune response in porcine intestinal epithelial and antigen presenting cells. (2014)
  • Author(s): Villena, J., H. Aso, H. Kitazawa et al.
  • Journal Title: BMC Microbiol. Volume: 14(126) Issue: 1 Pages: 1-14
  • DOI: 10.1186/1471-2180-14-126
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of the immunoregulatory capacities of feed microbial materia is in porcine intestinal immune and epithelial cells (2014)
  • Author(s): Kumagae, N., P. Kanmani, H. Kitazawa, et al.
  • Journal Title: Open J. Vet. Med. Volume: 4 Issue: 03 Pages: 15-28
  • DOI: 10.4236/ojvm.2014.43003
  • Peer Reviewed
• [Journal Article] <i>Bifidobacterium breve</i> MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect (2014)
  • Author(s): Murata, K., H. Kitazawa et al.
  • Journal Title: Bioscience of Microbiota, Food and Health Volume: 33 Issue: 1 Pages: 1-10
  • DOI: 10.12938/bmfh.33.1
  • NAID: 130004562680
  • ISSN: 2186-3342
  • Peer Reviewed
• [Journal Article] Modulation of intestinal TLR4-inflammatory signalling pathways by probiotic microorganisms: lessons learned from Lactobacillus jensenii TL2937. (2014)
  • Author(s): Villena, J., H. Kitazawa
  • Journal Title: Front. Immunol. Volume: 4 Pages: 1-12
  • DOI: 10.3389/fimmu.2013.00512
  • Peer Reviewed
• [Journal Article] Modulation of mucosal antiviral immune response by immunobiotic lactic acid bacteria – Part I: the intestinal mucosa. (2013)
  • Author(s): Villena, J., H. Kitazawa et al.
  • Journal Title: Microbial pathogens and strategies for combating them: science, technology and education Volume: 3 Pages: 1814-1821
  • Peer Reviewed
• [Journal Article] Immunoregulatory Effect of Bifidobacteria Strains in Porcine Intestinal Epithelial Cells through Modulation of Ubiquitin-Editing Enzyme A20 Expression. (2013)
  • Author(s): Tomosada, Y., H. Kitazawa, et al.
  • Journal Title: PLoS ONE Volume: 8(3) Issue: 3 Pages: 1-12
  • DOI: 10.1371/journal.pone.0059259
  • Peer Reviewed
• [Journal Article] Advanced application of porcine intestinal epithelial cells for the selection of immunobiotics modulating toll-like receptor 3-mediated inflammation (2012)
  • Author(s): Villena, J., H.Kitazawa, et al
  • Journal Title: J.Microbiol.Immunol.Infect. Volume: (未定)(印刷中) Issue: 6 Pages: 474-481
  • DOI: 10.1016/j.jmii.2012.04.005
  • Peer Reviewed
• [Journal Article] Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells (2012)
  • Author(s): Villena, J., H.Kitazawa, et al
  • Journal Title: Clin.Vac.Immunol. Volume: (未定)(印刷中) Issue: 7 Pages: 1038-1053
  • DOI: 10.1128/cvi.00199-12
  • Peer Reviewed
• [Presentation] Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after toll-like receptor 3 activation (2015)
  • Author(s): Hortensia Zelaya, Asuka Tada, Haruki Kitazawa, Julio Villena et al.
  • Organizer: The First International Joint Meeting between the Latin American Society for Immunodeficiencies (LASID), the Argentinean Society for Immunology (SAI), and the French Society for Immunology (SFI)
  • Place of Presentation: Buenos Aires, Argentina
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] ブタにおけるペプチドグリカン認識タンパク質ファミリーの発現とその調節 (2015)
  • Author(s): 飯田ひかる、麻生 久、齋藤忠夫、北澤春樹ら
  • Organizer: 日本畜産学会第120回大会
  • Place of Presentation: 酪農学園大学(北海道江別市)
  • Year and Date: 2015-09-11
• [Presentation] ブタ腸管由来樹状細胞におけるイムノバイオティクスの取り込み解析 (2015)
  • Author(s): 月田、麻生、齋藤、北澤ら
  • Organizer: 日本畜産学会第119回大会
  • Place of Presentation: 宇都宮市
  • Year and Date: 2015-03-27 – 2015-03-30
• [Presentation] 新規イムノバオティック評価指標の網羅的探索 (2015)
  • Author(s): 小林、麻生、齋藤、北澤ら
  • Organizer: 日本畜産学会第119回大会
  • Place of Presentation: 宇都宮市
  • Year and Date: 2015-03-27 – 2015-03-30
• [Presentation] ロタウイルスのウシ腸管上皮細胞感染系によるイムノバオティック評価系への応用 (2014)
  • Author(s): 小林、石塚、齋藤、北澤ら
  • Organizer: 日本食品免疫学会 第１０回学術大会
  • Place of Presentation: 東京（文京区）
  • Year and Date: 2014-10-16 – 2014-10-17
• [Presentation] Probiotics:Immunobiotics and Immunogenics. (2014)
  • Author(s): Kitazawa, H.
  • Organizer: CERELA-CONICET Seminar
  • Place of Presentation: Tucuman, Argentina
  • Year and Date: 2014-09-22
  • Invited
• [Presentation] Anti-inflammatory Ability of Plant derived Immunobiotic Lactobacillus delbrueckii subsp. delbrueckii TUA4408L and Its Immunogenic Extracellular Polysaccharides via Regulating TLR Signaling in Porcine Intestinal Epitheliocytes. (2014)
  • Author(s): Kanmani, P., H. Aso, T. Saito, H. Kitazawa et al.
  • Organizer: asm2014
  • Place of Presentation: Boston, USA
  • Year and Date: 2014-05-17 – 2014-05-20
• [Presentation] ブタ腸管上皮細胞におけるビフィズス菌のToll様受容体を介する抗炎症機構 (2014)
  • Author(s): 友定、北澤ら
  • Organizer: 日本畜産学会第118回大会
  • Place of Presentation: つくば市
• [Presentation] ブタ末梢血単球由来樹状細胞によるイムノバイオティック評価 (2014)
  • Author(s): 高橋、北澤ら
  • Organizer: 日本畜産学会第118回大会
  • Place of Presentation: つくば市
• [Presentation] Anti-inflammatory effect of bifidobacteria strains via modulation of TLR negative regulators in porcine intestinal epithelial cells. (2013)
  • Author(s): Tomosada, Y., H. Kitazawa et al.
  • Organizer: FEMS2013
  • Place of Presentation: ライプチヒ、ドイツ
• [Presentation] Immunobiotic evaluation of functional feed materials in porcine intestinal immune and epithelial cells. (2013)
  • Author(s): Kumagae, N., H. Kitazawa et al.
  • Organizer: FEMS2013
  • Place of Presentation: ライプチヒ、ドイツ
• [Presentation] ブタ末梢血由来樹状細胞の分化誘導とイムノバイオティック評価系への応用 (2013)
  • Author(s): 高橋、北澤ら
  • Organizer: 平成25年度酪農科学シンポジウム
  • Place of Presentation: 岡山市
• [Presentation] ブタ腸管由来樹状細胞の乳酸菌に対する自然免疫認識特性 (2013)
  • Author(s): 月田、北澤ら
  • Organizer: 平成25年度酪農科学シンポジウム
  • Place of Presentation: 岡山市
• [Presentation] 植物由来乳酸菌が生産する菌体外多糖による腸管炎症免疫調節機構 (2013)
  • Author(s): 友定、北澤ら
  • Organizer: 日本食品免疫学会第9回学術大会
  • Place of Presentation: 東京(文京区)
• [Presentation] ブタ末梢血由来樹状細胞の分化誘導とイムノバイオティック評価系への利用 (2013)
  • Author(s): 高橋、北澤, ら
  • Organizer: 日本畜産学会第116回大会
  • Place of Presentation: 広島市
• [Presentation] ブタの生産性を高めるイムノバイオティツク乳酸菌の抗病性効果 (2013)
  • Author(s): 須田、北澤, ら
  • Organizer: 日本畜産学会第116回大会
  • Place of Presentation: 広島市
• [Presentation] Role of pattern recognition receptors in the therapeutic effect of immunobiotics and immunogenics. (2012)
  • Author(s): Kitazawa, H.
  • Organizer: LVII Reunion Cientifica Anual de la Sociedad Argentina de Investigation Clinica, LX Reunion Cientifica Anual de la Sociedad Argentina de Inmunologia.
  • Place of Presentation: Mar del Plata, Argentina(招待講演)
• [Presentation] Lactobacillus jensenii TL2937 modula la expresion de reguladores negativos de TLR4 en celulas presentadoras de antigeno de intestino porcino a traves de TLR2. (2012)
  • Author(s): Villena, J., H. Kitazawa al.
  • Organizer: LVII Reunion Cientifica Anual de la Sociedad Argentina de Investigation Clinica, Lx Reunion Cientifica Anual de la Sociedad Argentina de Inmunologia.
  • Place of Presentation: Mar del Plata, Argentina
• [Book] Probiotics: Immunobiotics and Immunogenics (2013)
  • Author(s): Villena, J., S. Alvarez, H. Kitazawa (編集者)
  • Total Pages: 402
  • Publisher: CRC Press
• [Book] Probiotics:Sources, Types and Health Benefits. (2012)
  • Author(s): Villena, J., H. Kitazawa, et al.
  • Publisher: Nova Science Publishers, Inc.
• [Patent(Industrial Property Rights)] 腸管免疫の抑制剤のスクリーニング方法 (2015)
  • Inventor(s): 北澤、麻生ら
  • Industrial Property Rights Holder: (株)明治・東北大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-12-11
  • Acquisition Date: 2016-02-03
• [Patent(Industrial Property Rights)] プロバイオティクスの被貪食能の評価方法およびこれを利用したスクリーニング方法 (2015)
  • Inventor(s): 北澤、麻生ら
  • Industrial Property Rights Holder: (株)明治・東北大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-053877
  • Filing Date: 2015-03-17