Activation of epidermal growth factor receptor via CCR3 in bronchial epithelial cells
Activation of epidermal growth factor receptor via CCR3 in bronchial epithelial cells
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DOI：
10.1016/j.bbrc.2004.05.172
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发表时间：
2004-07-23
影响因子：
3.1
通讯作者：
Chihara, J
中科院分区：
文献类型：
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作者：
Adachi, T;Cui, CH;Chihara, J
我们先前发现支气管上皮细胞表达CCR 3，其信号传导激活丝裂原活化蛋白（MAP）激酶激活和细胞因子产生。一些研究人员已经关注癌细胞中G蛋白偶联受体（GPCR）和表皮生长因子受体（埃格）之间的信号串扰。在这项研究中，我们研究了EGFR在支气管上皮细胞系NCl-H-292中CCR 3信号传导中的作用。Eotaxin（1- 100 nM）诱导NCl-H-292细胞中埃格的剂量依赖性酪氨酸磷酸化。埃格抑制剂（AG 1478）预处理细胞可显著抑制Eotaxin诱导的MAP激酶磷酸化。嗜酸性粒细胞趋化因子刺激IL-8的产生，这是由AG 1478抑制。EGFR通过CCR 3的反式激活是激发支气管上皮细胞中MAP激酶激活和细胞因子产生的关键途径。阐明趋化因子的信号通路将有助于开发包括支气管哮喘在内的过敏性疾病的新的治疗策略。(C)2004年由Elsevier Inc.出版
We have previously found that bronchial epithelia] cells express CCR3 whose signaling elicits mitogen-activated protein (MAP) kinase activation and cytokine production. Several investigators have focused on the signaling crosstalk between G protein-coupled receptors (GPCRs) and epidermal growth factor receptor (EGER) in cancer cells. In this study, we investigated the role of EGFR in CCR3 signaling in the bronchial epithelial cell line NCl-H-292. Eotaxin (1-100nM) induced dose-dependent tyrosine phosphorylation of EGER in NCl-H-292 cells. Pretreatment of the cells with the EGER inhibitor (AG1478) significantly inhibited the MAP kinase phosphorylation induced by eotaxin. Eotaxin stimulated IL-8 production, which was inhibited by AG1478. The transactivation of EGFR through CCR3 is a critical pathway that elicits MAP kinase activation and cytokine production in bronchial epithelial cells. The delineation of the signaling pathway of chemokines will help to develop a new therapeutic strategy to allergic diseases including bronchial asthma. (C) 2004 Published by Elsevier Inc.