白细胞介素-1β刺激的细胞外信号调节激酶1/2（ERK1/2）和p38α丝裂原活化蛋白激酶（MAPK）的激活介导了人宫颈癌细胞系（HeLa细胞）中白细胞介素-6、白细胞介素-8和生长调节致癌基因α（GRO-α）的转录上调。
IL-1beta-stimulated activation of ERK1/2 and p38alpha MAPK mediates the transcriptional up-regulation of IL-6, IL-8 and GRO-alpha in HeLa cells.
作者信息
Yang Huei-Ting, Cohen Philip, Rousseau Simon
机构信息
MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee, DD1 5EH, United Kingdom.
出版信息
Cell Signal. 2008 Feb;20(2):375-80. doi: 10.1016/j.cellsig.2007.10.025. Epub 2007 Nov 7.
Epithelial cells represent the first line of defense against infection. Here we have studied the production of inflammatory mediators induced by IL-1beta in the HeLa epithelial cell line. We found that GRO-alpha, IL-6 and IL-8 were the only three inflammatory mediators elevated out of 36 tested. Specific inhibition of p38alpha MAP kinase or preventing the activation of ERK1/ERK2 partially reduced the production of these substances, while the combined blockade of both pathways almost abolished secretion. The suppression of these signaling pathways mainly reduced transcription of the genes encoding GRO-alpha, IL-6 and IL-8, rather than affecting mRNA stability, translation or secretion. The production of these three inflammatory mediators was shown to account for the ability of the HeLa cell culture medium to stimulate the migration of monocytes/macrophages, suggesting a key role for p38 MAPK and ERK1/ERK2 in orchestrating the epithelial cell response to infection.
上皮细胞是抵御感染的第一道防线。在此，我们研究了白细胞介素-1β（IL-1β）在人宫颈癌上皮细胞系（HeLa）中诱导产生的炎症介质。我们发现，在36种被测炎症介质中，只有生长调节致癌基因-α（GRO-α）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）这三种炎症介质水平升高。对p38α丝裂原活化蛋白激酶（MAP激酶）的特异性抑制或阻止细胞外信号调节激酶1/2（ERK1/ERK2）的激活可部分降低这些物质的产生，而同时阻断这两条信号通路几乎可完全消除其分泌。对这些信号通路的抑制主要降低了编码GRO-α、IL-6和IL-8的基因的转录，而非影响信使核糖核酸（mRNA）的稳定性、翻译或分泌。这三种炎症介质的产生被证明是HeLa细胞培养基刺激单核细胞/巨噬细胞迁移能力的原因，这表明p38丝裂原活化蛋白激酶（MAPK）和ERK1/ERK2在协调上皮细胞对感染的反应中起关键作用。
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