Establishment of in vitro gut inflammatory model and search and mechanism of food factor possessing anti-inflammatory activit y

• Project/Area Number: 21300276
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Eating habits, studies on eating habits
• Research Institution: Kobe University
• Principal Investigator: MIZUNO Masashi 神戸大学, 大学院・農学研究科, 教授 (00212233)
• Co-Investigator(Kenkyū-buntansha): NISHITANI Yosuke 神戸大学, 自然科学系先端融合研究環重点研究部, 助教 (80457093)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2009: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
• Keywords: 健康と食生活 / 炎症性腸疾患 / マクロファージ / インターロイキン-8 / レンチナン / エンドサイトーシス / 腫瘍壊死因子 / インターナリゼイション / キノコ / プロバイオティックス / インターフェロン-γ / ポリフェノール / 乳酸菌

Research Abstract

A system for assessing the anti-inflammatory effect of food factors has been developed by establishing a co-culture system with intestinal epithelial Caco-2 cells(apical side) and macrophage RAW264. 7 cells(basolateral side) stimulated with lipopolysaccharide. Curcumin and luteolin as polyphenols, fucoidan and lentinan as polysaccharide shows the anti-inflammatory activity in this system. Particularly, it was demonstrated that fucoidan indicated its activity by producing hydrogen peroxide from Caco-2 cells.

Research Products

• [Journal Article] β-Glucan from Lentinus edodes inhibits nitric oxide and tumor necrosis factor-□production and phosphorylation of mitogen-activated protein kinases in lipopolysaccharide-stimulated murine RAW 264. 7 (2012)
  • Author(s): Xu, X. J., Yasuda, M., Tsuruta, S., Mizuno, M., and Ashida, H.
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 871-878
  • Peer Reviewed
• [Journal Article] TLR ligands of Lactobacillus sakei LK-117 isolated from seed mash for brewing sake are potent inducers of IL-12 (2011)
  • Author(s): Masuda, Y., Takahashi, T., Yoshida, K., Nishitani, Y., Mizuno, M. and Mizoguchi, H.
  • Journal Title: J. Biosci. Bioeng. Volume: 112 Pages: 363-368
  • NAID: 110008761493
  • Peer Reviewed
• [Journal Article] Oral treatment with extract of Agaricus blazei Murill enhanced Th1 response through intestinal epithelial cells and suppressed OVA-sensitized allergy in mice (2011)
  • Author(s): Bouike, G., Nishitani, Y., Shiomi, H., Yoshida, M., Azuma, T., Hashimoto, T., Kanazawa, K. and Mizuno, M.
  • Journal Title: Evid. Based Complement. Alternat Volume: Volume Issue: 1 Pages: 11-11
  • DOI: 10.1155/2011/532180
  • Peer Reviewed
• [Journal Article] β-Glucan from lentinus edodes inhibits NO and TNF-α production and phosphorylation of mitogen-activated protein kinases in LPS-stimulated murine RAW 264.7 (2011)
  • Author(s): Xu, X.J., Yasuda, M., Tsuruta, S., Mizuno, M., Ashida, H.
  • Journal Title: Journal of Biological Chemistry Volume: 287(2) Pages: 871-878
  • Peer Reviewed
• [Journal Article] Anti-inflammatory activities of Lactococcus lactis subsp. cremoris FC in in vitro and in vivo gut inflammation (2010)
  • Author(s): Nishitani, Y. and Mizuno, M.
  • Journal Title: Biosci. Microflora Volume: 29 Pages: 169-178
  • Peer Reviewed
• [Journal Article] Membrane fusion process and assembly of cell wall during cytokinesis in the brown alga (2010)
  • Author(s): Nagasato, C., Inoue, A., Mizuno, M., Kanazawa, K., Ojima, T., Okuda, K. and Motomura, T.
  • Journal Title: Silvetia babingtonii Volume: 232 Pages: 287-298
  • Peer Reviewed
• [Journal Article] Lipoxin A4 reduces lipopolysaccharide-induced inflammation in macrophages and intestinal epithelial cells through inhibition of NF-kappaB activation (2010)
  • Author(s): Kure, I., Nishiumi, S., Nishitani, Y., Tanoue, T., Ishida, T., Mizuno, M., Fujita, T., Kutsumi, H., Arita, M., Azuma, T. and Yoshida, M.
  • Journal Title: J. Pharmacol. Exp. Ther. Volume: 332 Pages: 541-548
  • Peer Reviewed
• [Journal Article] Anti-inflammatory activities of Lactococcus lactis subsp.cremoris FC in in vitro and in vivo gut inflammation (2010)
  • Author(s): Nishitani, Y.Mizuno, M.
  • Journal Title: Biosci.Microflora Volume: 29(4) Pages: 169-178
  • Peer Reviewed
• [Journal Article] Oral treatment with extract of Agaricus blazei Murill enhanced Th1 response through intestinal epithelial cells and suppressed OVA-sensitized allergy in mice (2010)
  • Author(s): Bouike, G., Nishitani, Y., Shiomi, H., Yoshida, M., Azuma, T., Hashimoto, T., Kanazawa, K., Mizuno, M.
  • Journal Title: Evid.Based Complement. Altermat.Med. Volume: ID532180 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Different suppressive effects of fucoidan and lentinan on IL-8 mRNA expression in in vitro gut inflammation (2009)
  • Author(s): Mizuno, M., Nishitani, Y., Hashimoto, T. and Kanazawa, K.
  • Journal Title: Biosci. Biotech. Biochem. Volume: 73 Pages: 2324-2325
  • NAID: 10027547145
  • Peer Reviewed
• [Journal Article] Lactococcus lactis subsp. cremoris FC alleviates symptoms of colitis induced by dextran sulfate sodium in mice (2009)
  • Author(s): Nishitani, Y., Tanoue, T., Yamada, K., Ishida, T., Yoshida, M., Azuma, T. and Mizuno, M.
  • Journal Title: Int. Immunopharmacol. Volume: 9 Pages: 1444-1451
  • Peer Reviewed
• [Journal Article] The distribution and accumulation of fucoxanthin and its metabolites after oral-administration in mice (2009)
  • Author(s): Hashimoto, T., Ozaki, Y., Taminato, M., Das, S. K., Mizuno, M., Yoshimura, K., Maoka, T. and Kanazawa, K.
  • Journal Title: Br. J. Nutr Volume: 102 Pages: 242-248
  • NAID: 120001919651
  • Peer Reviewed
• [Journal Article] Anti-inflammatory effect of Bifidobacterium longum on macrophage-like THP-1 cells via epithelial cell Caco-2 (2009)
  • Author(s): Takizawa, R., Nishitani, Y., Mizuno, M. and Osawa, R.
  • Journal Title: Biosci. Microflora Volume: 28 Pages: 45-48
  • NAID: 10026974720
  • Peer Reviewed
• [Journal Article] Quantitation and localization of fucoidan in Laminaria japonica using a novel antibody (2009)
  • Author(s): Mizuno, M., Nishitani, Y., Tanoue, T., Matoba, Y., Ojima, T., Hashimoto, T. and Kanazawa, K.
  • Journal Title: Biosci. Biotech. Biochem Volume: 73 Pages: 335-338
  • Peer Reviewed
• [Journal Article] Lactococcus lactis subsp.cremoris FC alleviates symptoms of colitis induced by dextran sulfate sodium in mice (2009)
  • Author(s): Nishitani, Y., Tanoue, T., Yamada, K., Ishida, T., Yoshida, M., Azuma, T., Mizuno, M.
  • Journal Title: International Immunopharmacology 9 Pages: 1444-1451
  • Peer Reviewed
• [Journal Article] Different suppressive effects of fucoidan and lentinan on IL-8 mRNA expression in in vitro gut inflammation (2009)
  • Author(s): Mizuno, M., Nishitani, Y., Hashimoto, T., Kanazawa, K.
  • Journal Title: Bioscience, Biotechnology and Biochemistry 73 Pages: 2324-2325
  • NAID: 10027547145
  • Peer Reviewed
• [Presentation] レンチナンの腸管炎症抑制機構:小腸上皮様Caco-2細胞のTNFR1の局在性に及ぼす影響について (2012)
  • Author(s): 水野雅史
  • Organizer: 日本農芸化学会平成24年度大会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-24
• [Presentation] レンチナンの腸管炎症抑制効果:小腸上皮様Caco-2細胞のTNFR1の局在性に及ぼす影響について (2012)
  • Author(s): 西谷洋輔、水野雅史
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都好大学(京都府)
  • Year and Date: 2012-03-24
• [Presentation] Lentinan ameliorates gut inflammation in an in vivo and an in vitro model : a possible inhibition mechanism on IL-8 mRNA expression in intestinal epithelial cells (2011)
  • Author(s): Nishitani, Y., Zhang, L., Kanazawa, K., Mizuno, M.
  • Organizer: The 6th International Medicinal Mushroom Conferenee
  • Place of Presentation: クロアチア、ザグレブ
  • Year and Date: 2011-09-26
• [Presentation] Gut anti-inflammatory activity of lentinan : influence on IL-8 and TNFR1 expression in intestinal epithelial-like Caco-2 cells (2011)
  • Author(s): Nishitani, Y., Zhang, L., Mizuno, M.
  • Organizer: 16th European Carbohydrate Symposium
  • Place of Presentation: イタリア、ソレント
  • Year and Date: 2011-07-05
• [Presentation] Gut anti-inflammator activity of lentinan : influence on IL-8 and TNFR1 expression in intestinal epithelial-like Caco-2 cell (2011)
  • Author(s): Masashi Mizuno
  • Organizer: 16th European Carbohydrate Symposiu
  • Place of Presentation: Sorrento, Ital
  • Year and Date: 2011-07-04
• [Presentation] In vitro腸炎モデルのおけるレンチナンの炎症抑制機構の検討 (2011)
  • Author(s): 水野雅史
  • Organizer: 日本農芸化学会平成23年度大会
  • Place of Presentation: 京都
  • Year and Date: 2011-03-27
• [Presentation] Lentinan inhibits gut inflammation through alteration of TNFR1 distribution in intestinal epithelial cells (2011)
  • Author(s): Nishitani, Y., Zhang, L., Mizuno, M.
  • Organizer: International Conference and Exhibition on Nutraceuticals and Functional Foods
  • Place of Presentation: ロイトン札幌ホテル(北海道)
• [Presentation] Attenuation of the inflammatory response in a mouse colitis model by antioxidant luteolin : Key role of aglycone in inactivation of macrophages co-cultured with intestinal epithelial cells in vitro (2010)
  • Author(s): Yosuke Nishitani, Masashi Mizuno
  • Organizer: Society of Free Radical Biology and Medicine 17th Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2010-11-18
• [Presentation] In vivo腸管炎症モデルを用いたレンチナン経口投与の炎症性腸疾患抑制効果 (2010)
  • Author(s): 張玲、西谷洋輔、吉田優、東健、水野雅史
  • Organizer: 日本応用糖質科学会
  • Place of Presentation: 静岡県コンベンションアーツセンター(静岡県)
  • Year and Date: 2010-09-15
• [Presentation] 食用キノコであるガルガルの炎症性腸疾患抑制効果とその活性物質の分離 (2010)
  • Author(s): 渡部純也、原田栄津子、森園智浩、吉田美友紀、河岸洋和、水野雅史
  • Organizer: 日本食品科学工学会
  • Place of Presentation: 東京農業大学(東京都)
  • Year and Date: 2010-09-02
• [Presentation] βグルカンの機能性解明 (2010)
  • Author(s): 水野雅史
  • Organizer: 第3回 βグルカンシンポジウムin大阪
  • Place of Presentation: TKP大阪本町ビジネスセンター(大阪府)
  • Year and Date: 2010-03-12
• [Presentation] Suppressive effect of lentinan on IL-8 and TNFR1 mRNA expression in in vitro gut inflammation model (2009)
  • Author(s): Masashi Mizuno, Takeshi Tanoue, Yosuke Nishitani
  • Organizer: European Polysaccharide Network Of Excellence 2009
  • Place of Presentation: Turke、Finland
  • Year and Date: 2009-09-22
• [Presentation] Lactococcus lactis subsp.cremoris FC alleviates symptoms of colitisinduced by dextran sulfate sodium in mice (2009)
  • Author(s): Y.Nishitani, K.Kanazawa, M.Mizuno
  • Organizer: The Australian Society for Microbiology 2009
  • Place of Presentation: Perth、Australia
  • Year and Date: 2009-07-08
• [Book] プロバイオティクスの炎症性腸疾患抑制作用、免疫機能性食品の基礎と応用 (2010)
  • Author(s): 西谷洋輔、水野雅史
  • Publisher: シーエムシー出版
• [Book] βグルカン高含有食品素材の免疫賦活活性、βグルカンの基礎と応用-感染、抗がん、ならびに機能性食品へのβグルカンの関与- (2010)
  • Author(s): 水野雅史
  • Publisher: シーエムシー出版
• [Book] In vitro and in vivo immunnomodulatory and anti-allergic effects of Agaricus blazei Murill, In Dietary Components and Immune Functio (2010)
  • Author(s): Mizuno, M.
  • Publisher: Humana Pres
• [Book] In Dietary Components and Immune Function (2010)
  • Author(s): Mizuno, M.
  • Total Pages: 693
  • Publisher: Humana Press
• [Book] βグルカンの基礎と応用-感染、抗がん、ならびに機能性食品へのβグルカンの関与 (2010)
  • Author(s): 水野雅史
  • Total Pages: 283
  • Publisher: シーエムシー出版
• [Book] 免疫機能性食品の基礎と応用 (2010)
  • Author(s): 西谷洋輔、水野雅史
  • Total Pages: 227
  • Publisher: シーエムシー出版
• [Remarks]
  • URL: http://www.research.kobe-u.ac.jp/ans-glyco-chain/
• [Remarks]
  • URL: http://www.research.kobe-u.ac.jp/ans-glyco-chain/
• [Remarks]
  • URL: http://www.research.kobe-u.ac.jp/ans-glyco-chain/