Upregulation of MUC5AC Gene Expression by IL-4 Through CREB in Human Airway Epithelial Cells
Upregulation of MUC5AC Gene Expression by IL-4 Through CREB in Human Airway Epithelial Cells
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DOI：
10.1002/jcb.22330
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发表时间：
2009-11-01
影响因子：
4
通讯作者：
Song, Kyoung Seob
中科院分区：
文献类型：
--
作者：
Kim, Cheol Hong;Kim, Kyu-Earn;Song, Kyoung Seob
粘液高分泌是变态反应发病机制的重要特征。虽然已知白细胞介素（IL）-4是呼吸系统疾病中的炎症介质，但IL-4诱导MUC 5AC基因表达的机制尚未完全探索。本研究旨在探讨IL-4诱导气道MUC 5AC基因表达的机制。我们研究了丝裂原活化蛋白激酶（MAPK）信号转导对气道上皮MUC 5AC基因表达的作用。我们发现用IL-4处理细胞后，ERK 1/2磷酸化增加，而p38和JNK磷酸化未检测到。此外，ERK 1/2的药理学和遗传学抑制废除IL-4诱导的MUC 5AC基因表达。此外，我们研究了p90核糖体S6激酶1（RSK 1）作为ERK 1/2在IL-4信号传导中的下游信号传导靶点的激活。通过用PD 98059或表达MEK 1显性阴性突变体的质粒预处理来防止RSK 1的活化。我们还发现RSK 1介导了IL-4诱导的cAMP反应元件结合蛋白（CREB）的磷酸化和MUC 5AC的转录。此外，MUC 5AC启动子中的cAMP反应元件（CRE）似乎对于NCI-H292细胞中IL-4诱导的MUC 5AC基因表达是重要的。J.细胞。生物化学。108：974-981，2009年。(C)2009 Wiley-Liss，Inc.
Mucus hypersecretion is an important characteristic feature of the pathogenesis of allergy. Although interleukin (IL)-4 is known to be an inflammatory mediator in respiratory diseases, the mechanism by which IL-4 induces MUC5AC gene expression has not been fully explored. The aim of this study was to investigate the mechanism by which IL-4 induces MUC5AC gene expression in the airway. We examined the role of mitogen-activated protein kinase (MAPK) signaling on MUC5AC gene expression in airway epithelium. We showed that phosphorylation of ERK1/2 increased after treatment of cells with IL-4, whereas phosphorylation of p38 and JNK was not detected. In addition, pharmacologic and genetic inhibition of ERK1/2 abolished IL-4-induced MUC5AC gene expression. Moreover, we investigated the activation of p90 ribosomal S6 kinase 1 (RSK1) as a downstream signaling target of ERK1/2 in IL-4 signaling. The activation of RSK1 was prevented by pretreatment with PD98059 or plasmid expressing a MEK1 dominant-negative mutant. We also found that RSK1 mediated the IL-4-induced phosphorylation of cAMP response element-binding protein (CREB) and the transcription of MUC5AC. Furthermore, the cAMP-response element (CRE) in the MUC5AC promoter appears to be important for IL-4-induced MUC5AC gene expression in NCI-H292 cells. J. Cell. Biochem. 108: 974-981, 2009. (C) 2009 Wiley-Liss, Inc.