A novel anti-allergic property by food factor possessing high affinity lectin-like protein against IgE

• Project/Area Number: 18K19741
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Kobe University
• Principal Investigator: Mizuno Masashi 神戸大学, 農学研究科, 教授 (00212233)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Ⅰ型アレルギー / 腸上皮細胞 / ガレクチン９ / フコイダン / コンブ / アレルギー / 抗アレルギー / 海藻類 / TLR9 / 共培養 / アレルギー抑制 / Toll-like receptor 9 / 陰イオン交換クロマトグラフィー / イムノグロブリンE / 肥満細胞 / レクチン / 自然免疫

Outline of Final Research Achievements

To clarify the mechanism of Galectin 9 (Gal9) production by fucoidan administration, a culture system consisting of HT-29/RBL-2H3 cells was first constructed. It was demonstrated that the amount of Gal9 secreted to the basolateral side was increased with dose-dependent manner, and the amount of Gal9 secreted and Gal9 mRNA expression increased over time depending on the amount of fucoidan added. Furthermore, degranulation of RBL-2H3 cells was also suppressed. Next, to clarify the involvement of TLR9 as the fucoidan receptor, we evaluated its effect on Gal9 release using a TLR9 knockdown strain of HT-29 cells transfected with a TLR9 siRNA sequence. As a result, a decrease in the amount of Gal9 secreted to the basolateral side was observed upon TLR9 knockdown. In conclusion, we demonstrated that oral fucoidan suppresses type I allergy by producing Gal9 in the blood via TLR9 receptors expressed on intestinal epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

フコイダン経口摂取により、TLR9を介してIgE高親和性のガレクチン9が血中に分泌されるので、例えば既に花粉症などのアレルギー疾患を罹患した後でもその発症を抑制できることを示唆しており、これまでの抗アレルギー抑制機構とは全く異なった新規抑制機構を提唱できる。すなわち、これまでアレルギーを抑制する目的で着目されて来たTh1/Th2バランスの崩れを改善することを目的としていないため、細胞性あるいは体液性免疫への影響することなくアレルギーを改善できる可能性がある。

Research Products

• [Journal Article] Toll-like receptor 9 is involved in the induction of galectin-9 protein by dietary anti-allergic compound fucoidan (2023)
  • Author(s): Ezan Gnagnan J. E.、Mizuno Masashi
  • Journal Title: AIMS Allergy and Immunology Volume: 7 Issue: 1 Pages: 24-39
  • DOI: 10.3934/allergy.2023002
  • Peer Reviewed
• [Journal Article] Oral administration of fucoidan can exert anti-allergic activity after allergen sensitization by enhancement of galectin-9 secretion in blood (2020)
  • Author(s): Mizuno, M., Sakaguchi, K. and Sakane, I.
  • Journal Title: Biomolecules Volume: 10 Issue: 2 Pages: 258-258
  • DOI: 10.3390/biom10020258
  • NAID: 120006826807
  • Peer Reviewed / Open Access
• [Journal Article] Influence of Temperature on the Anti-allergic Activity of Fucoidan Extracted from <i>Saccharina japonica</i> (2019)
  • Author(s): Morita, A., Tanino, Y., Ojima, T. and Mizuno, M.
  • Journal Title: Food Science and Technology Research Volume: 25 Issue: 4 Pages: 607-611
  • DOI: 10.3136/fstr.25.607
  • NAID: 130007715857
  • ISSN: 1344-6606, 1881-3984
  • Peer Reviewed
• [Presentation] TLR9 is involved in fucoidan-induced galectin-9 upregulation in vitro (2023)
  • Author(s): EZAN EPIPHANIE、MIZUNO MASASHI
  • Organizer: 日本農芸化学会関西支部例会
• [Presentation] 加熱処理によるフコイダン分解物の抗アレルギー効果への影響 (2020)
  • Author(s): 森田温子、水野雅史
  • Organizer: 日本農芸化学会2020年度大会
• [Presentation] 276.Structural change of fucoidan extracted from Saccharina japonica by heat treatment and its anti-allergy property (2019)
  • Author(s): Masashi Mizuno, Atsuko Morita, Ken-ichiro Minato
  • Organizer: 30th Annual Conference of the Australasian Society of Clinical Immunology and Allergy
  • Int'l Joint Research
• [Presentation] フコイダンが有する抗アレルギー効果の安定性について (2019)
  • Author(s): 森田温子、水野雅史
  • Organizer: 日本応用糖質科学会平成31年度大会