Prediction of onset of allergic diseases through analysis of single nucleotide polymorphisms and prevention of onset of allergic diseases by an appropriate intake of flavonoids

通过单核苷酸多态性分析预测过敏性疾病的发病，并通过适当摄入黄酮类化合物预防过敏性疾病的发病

• 批准号: 17591040
• 负责人: TANAKA Toshio
• 金额: $ 2.11万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591040/
• 关键词: allergy; prevention; gene polymorphism; complementary and alternative medicine; 予防; フラボノイド

Since the prevalence of allergic diseases has increased dramatically during the last two decades, it is essential to reveal factors that are responsible for the increase and to develop strategies to prevent the onset of allergic diseases.It was found that a novel IL-18 gene polymorphism, IL-18-105A/C was associated with asthma. There was a significant linkage disequilibrium between IL-18-105A/C and IL-18--137G/C which was previously demonstrated to affect IL-18 gene transcription. Moreover, the IL-18 production by purified monocytes in response to LPS or A23187+PMA from volunteers with 105A/A or -137G/G genotype was higher than that with 105A/C or -137G/C genotype, respectively. Therefore, it was suggested that the genetic capacity to produce more IL-18 may have an influence on the onset of asthma.Flavonoids including fisetin, luteolin and apigenin inhibited not only IL-4 and IL-13 synthesis but also CD40 ligand expression by activated basophils. Since at least two signals through IL-4 or IL-13 receptor and through CD40 are required for B cells to differentiate into IgE secreting cells, flavonoids are considered to a natural IgE inhibitor. Luteolin suppressed AP-1 activation without any inhibition of MAPK family by basophils. Furthermore, analyses of inhibitory activity of 45 flavones and related compounds on the IL-4 synthesis by basophils determined a fundamental structure for the inhibition, leading to make a novel flavonoid, that is anticipated to possess high activity and high absorption. Thus this evidence will be helpful for the development of low molecular compounds for allergic diseases and it is expected that a dietary menu including an appropriate intake of flavonoids may provide a form of complementary and alternative medicine and a preventative strategy for allergic diseases. Clinical studies to verify these points are now tested.

由于过敏性疾病的发病率在过去20年中急剧上升，因此有必要揭示导致过敏性疾病增加的因素，并制定预防过敏性疾病发生的策略。IL-18-105A/C和IL-18-137G/C之间存在着显著的连锁不平衡，这一连锁不平衡影响了IL-18基因的转录。此外，携带105A/A或-137G/G基因型者的纯化单核细胞在内毒素或A23187+PMA刺激下产生IL-18的能力分别高于携带105A/C或-137G/C基因型者。黄酮类化合物包括非瑟素、木犀草素和芹菜素不仅能抑制IL-4和IL-13的合成，而且还能抑制嗜碱性粒细胞CD40配体的表达。由于B细胞至少需要通过IL-4或IL-13受体和CD40两种信号才能分化为IgE分泌细胞，因此类黄酮类化合物被认为是一种天然的IgE抑制剂。木犀草素可抑制AP-1的活化，但不影响嗜碱性粒细胞对MAPK家族的作用。此外，通过对45个黄酮类及相关化合物对嗜碱性粒细胞合成IL-4的抑制活性的分析，确定了抑制的基本结构，从而合成了一种新的黄酮类化合物，有望具有高活性和高吸收能力。因此，这一证据将有助于开发治疗过敏性疾病的低分子化合物，预计包括适当摄取类黄酮的饮食菜单可能提供一种形式的补充和替代药物，以及预防过敏性疾病的策略。验证这些观点的临床研究现在得到了检验。

项目成果

アレルギーとフラボノイド

过敏和类黄酮

• 发表时间: 2006
• 期刊: 日本補完代替医療学会誌 3
• 作者: 田中敏郎;他
• 通讯作者: 他

Allergy and flavonoids.

过敏和类黄酮。

• 发表时间: 2006
• 期刊: Japanese Journal of Complementary and Alternative Medicine 3
• 作者: T.anaka;et al.
• 通讯作者: et al.

Flavonoids and related compounds as anti-allergic substances.

• DOI: 10.2332/allergolint.r-06-135
• 发表时间: 2007-11
• 期刊: Allergology international : official journal of the Japanese Society of Allergology
• 作者: M. Kawai;T. Hirano;S. Higa;J. Arimitsu;Michiru Maruta;Y. Kuwahara;T. Ohkawara;K. Hagihara;T. Yamadori;Y. Shima;A. Ogata;I. Kawase;Toshio Tanaka

Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human basophils

• DOI: 10.1159/000092554
• 发表时间: 2006-01-01
• 期刊: INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
• 影响因子: 2.8
• 作者: Hirano, Toru;Arimitsu, Junsuke;Tanaka, Toshio
• 通讯作者: Tanaka, Toshio

アレルギー疾患とフラボノイド

过敏性疾病和类黄酮

• 发表时间: 2006
• 期刊: Foods ＆ Food Ingredients Journal of Japan 211
• 作者: 田中敏郎;他
• 通讯作者: 他