Celastrol binds to ERK and inhibits FcεRI signaling to exert an anti-allergic effect

被引：50

作者：

Kim, Youngmi ^{[1
]}

Kim, Kyungjong ^{[1
]}

Lee, Hansoo ^{[1
]}

Han, Sanghwa ^{[1
]}

Lee, Yun-Sil ^{[2
]}

Choe, Jongseon ^{[3
]}

Kim, Young-Myeong ^{[3
]}

Hahn, Jang-Hee ^{[3
]}

Ro, Jai Youl ^{[4
]}

Jeoung, Dooil ^{[1
]}

机构：

[1] Kangwon Natl Univ, Sch Biol Sci, Coll Nat Sci, Chunchon 200701, South Korea

[2] Korea Inst Radiol & Med Sci, Lab Radiat Effect, Div Radiat Biol, Seoul 139706, South Korea

[3] Kangwon Natl Univ, Sch Med, Chunchon 200701, South Korea

[4] Sungkyunkwan Univ, Sch Med, Suwon 440746, South Korea

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2009年 / 612卷 / 1-3期

关键词：

Allergic inflammation; Celastrol; Extracellular regulated kinase; Heat shock protein 90; Fc epsilon RI; ALLERGIC AIRWAY INFLAMMATION; HEAT-SHOCK; IN-VIVO; KINASE; ACTIVATION; EXPRESSION; CELLS; DEGRANULATION; INDUCTION; COMPLEX;

D O I：

10.1016/j.ejphar.2009.03.071

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：131 / 142

页数：12

共 48 条

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