Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IκB-NF-κB signaling pathways
Naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs-AP-1 and IKKs-IκB-NF-κB signaling pathways
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柚皮素通过抑制 MAPKs-AP-1 和 IKKs-IκB-NF-κB 信号通路的合作活动，减少 EGF 诱导的 A549 细胞 MUC5AC 分泌
DOI：
10.1016/j.ejphar.2012.06.040
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发表时间：
2012-09-05
影响因子：
5
通讯作者：
Su, Wei-wei
中科院分区：
文献类型：
--
作者：
Nie, Yi-chu;Wu, Hao;Su, Wei-wei
柚苷元（Naringenin）是柚苷的糖苷配基，已报道通过EGFR-PI 3 K-Akt/ERK MAPK信号通路抑制核因子κ B（NF-κ B B）的活性来减弱MUC 5AC的分泌。然而，先前的研究表明MUC 5AC启动子位于两个不同的区域：激活蛋白-1（AP-1）结合位点和NF-κ B结合位点。本研究全面地确定了MAPKs/AP-1和IKKs/I kappa B/NF-kappa B在表皮生长因子（EGF）诱导的A549细胞中的参与，并试图确定柚苷抑制EGF诱导的MUC 5AC分泌的信号通路。结果表明，100 μ M的柚皮苷不仅显著降低EGF诱导的A549细胞中MUC 5AC粘蛋白和mRNA的过度表达，而且抑制EGF受体、p38丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶（ERK 1/2）和c-Jun N-末端激酶（JNK）以及核NF-κ B p65和AP-1的磷酸化。此外，三种MAPK抑制剂（PD 98059、SB 203580和SP 600125）中的任一种显著抑制EGF诱导的MUC 5AC分泌。与MG 132相比，SN 50的抑制剂kappa B（I kappa B）磷酸化抑制剂在减少EGF诱导的MUC 5AC分泌方面更有效，因为抑制了核AP-1。同时，与柚苷相比，SP 600125和阿奇霉素在抑制EGF诱导的MUC 5AC分泌方面效果较差，因为核NF-κ B p65未改变。这些结果表明，柚苷通过抑制MAPKs/AP-1和IKKs/I κ B/NF-κ B信号通路的协同活性来减弱EGF诱导的A549细胞MUC 5AC分泌。(C)2012爱思唯尔有限公司版权所有。
Naringenin, the aglycone of naringin, has been reported to attenuate MUC5AC secretion by inhibiting activity of nuclear factor kappa B (NF-kappa B) via EGFR-PI3K-Akt/ERK MAPKinase signaling pathways. However, previous studies demonstrated that the MUC5AC promoter was located in two different regions: an activator protein-1 (AP-1) binding site and a NF-kappa B binding site. The current study comprehensively determined the involvement of MAPKs/AP-1 and IKKs/I kappa B/NF-kappa B in epidermal growth factor (EGF)-induced A549 cells, and sought to ascertain the signaling pathways of naringin imparted in suppression of EGF-induced MUC5AC secretion. The results showed that naringin of 100 mu M not only significantly decreased EGF-induced overexpressions of both MUC5AC mucin and mRNA in A549 cells, but also suppressed the phosphorylation of EGF receptor, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK), as well as nucleus NF-kappa B p65 and AP-1. Moreover, any of three MAPKs inhibitors (PD98059, SB203580, and SP600125) significantly inhibited EGF-induced MUC5AC secretion. And as compared to MG132, the inhibitor kappa B (I kappa B) phosphorylation inhibitor of SN50 was more effective in reducing EGF-induced MUC5AC secretion because of suppression of nucleus AP-1. Meanwhile, as compared to naringin, both SP600125 and azithromycin were less effective in suppressing EGF-induced secretion of MUC5AC because of the unchanged nucleus NF-kappa B p65. These results indicated that naringin attenuates EGF-induced MUC5AC secretion in A549 cells by suppressing the cooperative activities of MAPKs/AP-1 and IKKs/I kappa B/NF-kappa B signaling pathways. (C) 2012 Elsevier B.V. All rights reserved.