A yeast-based screening system identified bakkenolide B contained in Petasites japonicus as an inhibitor of interleukin-2 production in a human T cell line
A yeast-based screening system identified bakkenolide B contained in Petasites japonicus as an inhibitor of interleukin-2 production in a human T cell line
复制标题
基于酵母的筛选系统鉴定出 Petasites japonicus 中含有的 bakkenolide B 是人类 T 细胞系中白细胞介素 2 生成的抑制剂
DOI：
10.1093/bbb/zbab130
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Yano A
中科院分区：
文献类型：
--
作者：
Uesugi S;Hakozaki M;Kanno Y;Takahashi H;Kudo Y;Kimura K;Yamada H;Yano A
Ca 2+信号传导与各种疾病有关，如过敏、糖尿病和癌症。本研究利用酵母菌筛选方法对天然资源中的Ca 2+信号抑制剂进行了筛选，并利用YNS 17菌株（zds 1 Δ erg 3 Δ pdr 1/3Δ）从可食用野生植物蜂斗菜的花蕾中筛选到了bakkenoprotein B。Bakkengland B表现出对YNS 17菌株的生长恢复活性，并诱导野生型酵母细胞的Li+敏感性，表明其抑制钙调磷酸酶途径。此外，bakkenetrin B在Jurkat细胞（一种人T细胞系）中在基因和蛋白水平上抑制白细胞介素-2的产生，但不抑制人重组钙调神经磷酸酶（白细胞介素-2产生的上游调节因子）的体外磷酸酶活性。此外，与bakkenoprotein B相比，bakkenoprotein A在YNS 17和Jurkat细胞中显示出弱活性。这些结果揭示了新的生物学效应和P中所含巴肯内酯的构效关系。japonicusas的抑制剂白细胞介素-2生产的人T细胞。
Ca2+signaling is related to various diseases such as allergies, diabetes, and cancer. We explored Ca2+signaling inhibitors in natural resources using a yeast-based screening method and found bakkenolide B from the flower buds of edible wild plant,Petasites japonicus, using the YNS17 strain (zds1Δerg3Δpdr1/3Δ). Bakkenolide B exhibited growth-restoring activity against the YNS17 strain and induced Li+sensitivity of wild-type yeast cells, suggesting that it inhibits the calcineurin pathway. Additionally, bakkenolide B inhibited interleukin-2 production at gene and protein levels in Jurkat cells, a human T cell line, but not thein vitrophosphatase activity of human recombinant calcineurin, an upstream regulator of interleukin-2 production. Furthermore, bakkenolide A showed weak activity in YNS17 and Jurkat cells compared with bakkenolide B. These findings revealed new biological effects and the structure–activity relationships of bakkenolides contained inP. japonicusas inhibitors of interleukin-2 production in human T cells.