Development of non-allergic peptide preparation having mucosal immunostimulatory ability

具有粘膜免疫刺激能力的非过敏性肽制剂的研制

• 批准号: 13660266
• 负责人: OTANI Hajime
• 金额: $ 2.3万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660266/
• 关键词: casein phosphopeptides; IgA-stimulatory peptide; anti-allergic peptides; casein digests; SerP-X-SerP; immunoenhancing peptide; phosphorylated dextrin; functional foodstuffs; 経口摂取; 免疫促進; 非アレルゲン性; 腸管免疫; IgA; 機能性食品事材; ジホスホトリペプチド

Results obtained in the present investigation were summarized as follows:1) Dietary casein phosphopeptides reduced atopic dermatitis in NC mice via the enhancement of mucosal IgA levels and the reduction of serum IgE levels specific to allergens.2) The immunoregulatory activity of casen phosphopeptides was confirmed to be attributable to the sequence SerP-X-SerP.3) SerP-SerP-SerP obviously reacted with an antibody specific to phosphoserine-rich region of casein phosphopeptides whereas SerP-Leu-SeP was inert. These results suggested that SerP-X-SerP (X is not SerP) was non-allergic IgA-stimulatory peptide.4) Bovine casein was digested with 14 kinds of proteases, which are permitted to use as food supplements, and casein phosphopeptides were recovered from the digests. Casein phosphopeptides preparation obtained from caseins digested with proteases from Aspergillus oryzae had high stimulatory effect on IgA production and little reactivity with the antibody specific to phosphoserine-rich region of casein phosphopeptides. These facts suggested that the casein phosphopeptide preparation obtained from caseins digested with proteases from Aspergillus oryzae was non-allergic IgA-stimulatory peptide.5) In general, a dextrin consisting of 15 to 16 glucoses is considered to be non-allergic. On the other hand two phosphate groups is essential to display IgA-stimulatory effect of casein phosphopeptides. Hence, dextrins covalently coupled with 5 to 7 phosphate groups were prepared. The phosphorylated dextrin sitmulated IgA production in mouse spleen cell cultures. Moreover, the intestinal IgA level to pathogenic bacteria orally ingested was increased significantly when mice were given a diet containing phosphorylated dextrin for 35 days. These results suggest that phosphorylated dextrin is another non-allereic lgA-stimulatorv substance.

本研究的结果如下：1)酪蛋白磷酸肽通过提高粘膜中的IgA水平和降低变态反应原特异性的血清中的IgE水平来减轻NC小鼠的特应性皮炎。2)Casen磷酸肽的免疫调节活性与序列SERP-X-SerP有关。3)SERP-SERP明显地与酪蛋白磷酸肽富含丝氨酸区域的抗体发生反应，而SERP-Leu-Sep则不明显。这些结果表明，SERP-X-SERP(X不是SERP)是一种非过敏性的IgA刺激性多肽。4)用14种允许作为食品添加剂的酶消化牛酪蛋白，并从消化液中回收酪蛋白磷酸肽。米曲霉蛋白酶消化酪蛋白制备的酪蛋白磷酸肽对IgA的产生有很高的刺激作用，与酪蛋白磷酸肽富含丝氨酸区域的抗体反应较弱。这些事实表明，用米曲霉的蛋白酶消化酪蛋白得到的酪蛋白磷酸肽是非过敏性的IgA刺激性多肽。5)一般来说，由15-16个葡萄糖组成的糊精被认为是非过敏性的。另一方面，两个磷酸基团对于展示酪蛋白磷酸肽的免疫球蛋白A刺激作用是必不可少的。因此，制备了与5~7个磷酸基团共价偶联的糊精。磷酸化糊精可诱导小鼠脾细胞产生IgA。此外，口服含有磷酸化糊精的饲料35天后，小鼠肠道对致病菌的免疫球蛋白A水平显著升高。这些结果表明，磷酸化糊精是另一种非变异型LGA刺激物。

项目成果

Otani H.: "Immunomodulatory action as a novel physiological activity of casein phosphopeptide molecules"New food Industry. 44(8). 1-10

Otani H.：“免疫调节作用作为酪蛋白磷酸肽分子的新型生理活性”新食品工业。

Otani H. et al.: "Effects of bovine β-casein (1-28) and its chemically synthesized partial fragments on proliferative responses and immunoglobulin production in mouse spleen cell cultures"Biosci. Biotechnol. Biochem.. 65(11). 2489-2495 (2001)

Otani H. 等人：“牛 β-酪蛋白 (1-28) 及其化学合成的部分片段对小鼠脾细胞培养物中增殖反应和免疫球蛋白产生的影响”Biosci.Biochem. 65(11)。 -2495 (2001)

大谷 元: "カゼインホスホペプチドは腸管IgA産生を促進する!"化学と生物. 41(印刷中). (2003)

Hajime Otani：“酪蛋白磷酸肽促进肠道 IgA 的产生！”化学与生物学（2003 年）。

Zhang, F.M., Otani, H.: "Immunogenicity and antigenicity of casein phosphopeptides"Milchwissenschaft. 58(1/2). 9-13 (2003)

张，F.M.，大谷，H.：“酪蛋白磷酸肽的免疫原性和抗原性”Milchwissenschaft。

Hosono, A, Otani, H.et al.: "Impact of fermented milk on human health : Cholesterol-lowering and immunomodulatory properties of fermented milk"Animal Science Journal. 73(4). 242-256 (2002)

Hosono, A, Otani, H.等人：“发酵乳对人类健康的影响：发酵乳的降低胆固醇和免疫调节特性”动物科学杂志。