Stem cell factor-mediated activation pathways promote murine eosinophil CCL6 production and survival
Stem cell factor-mediated activation pathways promote murine eosinophil CCL6 production and survival
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DOI：
10.1189/jlb.0906595
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发表时间：
2007-04-01
影响因子：
5.5
通讯作者：
Lukacs, Nicholas W.
中科院分区：
文献类型：
--
作者：
Dolgachev, Vladislav;Thomas, Molly;Lukacs, Nicholas W.
过敏性疾病期间嗜酸性粒细胞的激活对病理生理反应的产生具有有害作用。干细胞因子（SCF）最近显示出对嗜酸性粒细胞的炎症、基因激活作用，并有助于过敏反应期间气道病理生理变化的产生。本研究中的数据概述了 SCF 在嗜酸性粒细胞中诱导的信号转导事件，并进一步证明 MEK 介导的信号通路对于 SCF 诱导的 CCL6 趋化因子激活和嗜酸性粒细胞存活至关重要。 SCF 介导的 cosinophil 激活包括 PI-3K 激活以及 MEK/MAPK 磷酸化途径。随后在存在或不存在特定途径抑制剂的情况下对 SCF 诱导的 CCL6 基因激活和产生进行的分析表明，MEK/MAPK 途径而非 PI-3K 途径对于 SCF 诱导的 CCL6 基因激活至关重要。这些相同的信号通路被证明可以启动抗凋亡事件并促进嗜酸性粒细胞存活，包括 BCL2 和 BCL3 的上调。总而言之，SCF 似乎是一种有效的嗜酸性粒细胞激活和存活因子。
Eosinophil activation during allergic diseases has a detrimental role in the generation of pathophysiologic responses. Stem cell factor (SCF) has recently shown an inflammatory, gene-activating role on eosinophils and contributes to the generation of pathophysiologic changes in the airways during allergic responses. The data in the present study outline the signal transduction events that are induced by SCF in eosinophils and further demonstrate that MEK-mediated signaling pathways are crucial for SCF-induced CCL6 chemokine activation and eosinophil survival. SCF-mediated cosinophil activation was demonstrated to include PI-3K activation as well as MEK/MAPK phosphorylation pathways. Subsequent analysis of CCL6 gene activation and production induced by SCF in the presence or absence of rather specific inhibitors for certain pathways demonstrated that the MEK/MAPK pathway but not the PI-3K pathway was crucial for the SCF-induced CCL6 gene activation. These same signaling pathways were shown to initiate antiapoptotic events and promote eosinophil survival, including up-regulation of BCL2 and BCL3. Altogether, SCF appears to be a potent cosinophil activation and survival factor.