Celastrol binds to ERK and inhibits FcεRI signaling to exert an anti-allergic effect
Celastrol binds to ERK and inhibits FcεRI signaling to exert an anti-allergic effect
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DOI：
10.1016/j.ejphar.2009.03.071
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发表时间：
2009-06-10
影响因子：
5
通讯作者：
Jeoung, Dooil
中科院分区：
文献类型：
--
作者：
Kim, Youngmi;Kim, Kyungjong;Jeoung, Dooil
雷公藤红素是一种从中国“神藤之雷”前提取的三萜类化合物，研究了其在过敏性炎症中的作用。雷公藤红素抑制抗原刺激的RBL2H3细胞分泌β-己糖苷酶，减少组胺释放，减少Th2细胞因子的表达，减少钙离子内流和细胞黏附。雷公藤红素作用于RBL2H3细胞后，ERK活性降低，ERK活性降低，ERK活性降低。分子动力学模拟表明雷公藤红素与ERK2上的一个大口袋结合，这是ATP结合的部位。雷公藤红素抑制免疫球蛋白Fc epsilon受体1(Fc Epsilon RL Gamma)与ERK的相互作用，并抑制Fc epsilon RL Gamma与蛋白激酶C Delta(PKC Delta)的相互作用。抗原刺激可诱导Rac1与ERK之间的所有相互作用，也可诱导Rac1与PKC Delta之间的所有相互作用。在抗原刺激的RBL2H3细胞中，抑制ERK可降低Rac I活性，抑制rac1可降低ERK活性。雷公藤红素通过抑制PKCα、PKCβ而调节上皮-间充质转化相关蛋白的表达。和抗原刺激的RBL2H3细胞中的rac1。雷公藤多醇可抑制抗原刺激的RBL2H3细胞的PKC Delta活性。雷公藤红素通过抑制热休克蛋白90(HSP90)与蛋白质之间的相互作用，对Fc epsilon RLβ信号转导产生负性影响。如Fc epsilon RLβ、Akt和PKCα。雷公藤红素对2，4-二硝基氟苯(DNFB)诱导的异位性皮炎有负性作用，需要ERK。雷公藤红素对佛波醇肉豆蔻酸酯(PMA)诱导的Balb/c小鼠皮肤炎症有明显的抑制作用。综上所述，雷公藤红素可与ERK结合，抑制Fc epsilon R1信号转导，发挥抗炎作用。(C)2009爱思唯尔B.V.保留所有权利。
The role of celastrol, a triterpene extracted front the Chinese "Thunder of God Vine," in allergic inflammation was investigated. Celastrol decreased the secretion of beta-hexosaminidase, decreased the release of histamine, decreased the expression of Th2 cytokines and decreased calcium influx and cell adhesion in antigen-stimulated RBL2H3 cells. Exposure to celastrol decreased the phosphorylation of extracellular regulated kinase (ERIO and the ERK kinase activity was decreased in RBL2H3 cells. A molecular dynamics simulation showed binding of celastrol to a large pocket in ERK2, which serves as the ATP-binding site. Exposure to celastrol inhibited the interaction between immunoglobulin Fc epsilon receptor 1 (Fc epsilon Rl gamma) and ERK and inhibited interaction between Fc epsilon Rl gamma and protein kinase C delta (PKC delta). Antigen stimulation induced all interaction between Rac1 and ERK as well as ail interaction between Rac1 and PKC delta. Inhibition ERK decreased Rac I activity and inhibition of Rac1 decreased ERK activity ill antigen-stimulated RBL2H3 cells. Celastrol regulated the expression of epithelial-mesenchymal transition (EMT)-related proteins through inhibition of PKC alpha., PKC delta. and Rac1 in antigen-stimulated RBL2H3 cells. Exposure to celatrol inhibited PKC delta activity in antigen-stimulated RBL2H3 cells. Celastrol exerted a negative effect on Fc epsilon Rl beta signaling by inhibiting the interaction between heat shock protein 90 (hsp90) and proteins. such as, Fc epsilon Rl beta, Akt and PKC alpha. Celastrol exerted a negative effect oil in vivo atopic dermatitis induced by 2, 4-dinitroflurobenzene (DNFB), which requires ERK. Celastrol also showed all inhibitory effect on skin inflammation induced by phorbol myristate acetate (PMA) in Balb/c mice. In summary, celastrol binds to ERK and inhibits Fc epsilon R1 signaling to exert an anti-inflammatory effect. (C) 2009 Elsevier B.V. All rights reserved.