Maeda-Yamamoto Mari, Inagaki Naoki, Kitaura Jiro, Chikumoto Takao, Kawahara Hiroharu, Kawakami Yuko, Sano Mitsuaki, Miyase Toshio, Tachibana Hirofumi, Nagai Hiroichi, Kawakami Toshiaki
National Institute of Vegetable and Tea Science, National Agriculture Research Organization, and School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
J Immunol. 2004 Apr 1;172(7):4486-92. doi: 10.4049/jimmunol.172.7.4486.
Tea contains a variety of bioactive compounds. In this study, we show that two O-methylated catechins, (-)-epigallocatechin-3-O-(3-O-methyl) gallate and (-)-epigallocatechin-3-O-(4-O-methyl) gallate, inhibit in vivo mast cell-dependent allergic reactions more potently than their nonmethylated form, (-)-epigallocatechin-3-O-gallate. Consistent with this, these O-methylated catechins inhibit IgE/Ag-induced activation of mouse mast cells: histamine release, leukotriene release, and cytokine production and secretion were all inhibited. As a molecular basis for the catechin-mediated inhibition of mast cell activation, Lyn, Syk, and Bruton's tyrosine kinase, the protein tyrosine kinases, known to be critical for early activation events, are shown to be inhibited by the O-methylated catechins. In vitro kinase assays using purified proteins show that the O-methylated catechins can directly inhibit the above protein tyrosine kinases. These catechins inhibit IgE/Ag-induced calcium response as well as the activation of downstream serine/threonine kinases such as Akt and c-Jun N-terminal kinase. These observations for the first time have revealed the molecular mechanisms of antiallergic effects of tea-derived catechins.
茶含有多种生物活性化合物。在本研究中，我们发现两种O-甲基化儿茶素，（-）-表没食子儿茶素-3-O-（3-O-甲基）没食子酸酯和（-）-表没食子儿茶素-3-O-（4-O-甲基）没食子酸酯，在体内比其未甲基化形式（-）-表没食子儿茶素-3-O-没食子酸酯更有效地抑制肥大细胞依赖性过敏反应。与此一致的是，这些O-甲基化儿茶素抑制IgE/Ag诱导的小鼠肥大细胞活化：组胺释放、白三烯释放以及细胞因子的产生和分泌均受到抑制。作为儿茶素介导的肥大细胞活化抑制的分子基础，已知对早期活化事件至关重要的蛋白酪氨酸激酶Lyn、Syk和布鲁顿酪氨酸激酶被O-甲基化儿茶素抑制。使用纯化蛋白进行的体外激酶测定表明，O-甲基化儿茶素可直接抑制上述蛋白酪氨酸激酶。这些儿茶素抑制IgE/Ag诱导的钙反应以及下游丝氨酸/苏氨酸激酶如Akt和c-Jun氨基末端激酶的活化。这些观察首次揭示了茶源儿茶素抗过敏作用的分子机制。
