Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca^2 + mobilization

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• 作者：Meichun Yuan ; Jianjie Li ; Jingzhang Lv ; Xucheng Mo ; Chengbin Yang ; Xiangdong Chen ; Zhigang Liu ; Jie Liu
• 关键词：PD ; polydatin ; CRACs ; calcium release-activated calcium channels ; PCA ; passive cutaneous anaphylaxis ; TG ; thapsigargin ; ER ; endoplasmic reticulum ; Fc¦ÅRI ; high-affinity IgE receptors ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; ROS
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2012
• 出版时间：1 November, 2012
• 年：2012
• 卷：264
• 期：3
• 页码：462-469
• 全文大小：637 K

文摘

Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (Fc¦ÅRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30 min suppressed Fc¦ÅRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased Fc¦ÅRI-mediated Ca^2 + increase in mast cells. The suppressive effects of PD on Fc¦ÅRI-mediated Ca^2 + increase were largely inhibited by using LaCl₃ to block the Ca^2 + release-activated Ca^2 + channels (CRACs). Furthermore, PD significantly inhibited Ca^2 + entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of Fc¦ÅRI-induced intracellular Ca^2 + influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing Fc¦ÅRI-induced Ca^2 + mobilization mainly through inhibiting Ca^2 + entry via CRACs, thus exerting a protective effect against PCA.