Pivotal role of c-Fos in nitric oxide synthase 2 expression in airway epithelial cells.
Pivotal role of c-Fos in nitric oxide synthase 2 expression in airway epithelial cells.
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DOI：
10.1016/j.niox.2008.12.004
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Erzurum SC
中科院分区：
文献类型：
--
作者：
Chambellan A;Leahy R;Xu W;Cruickshank PJ;Janocha A;Szabo K;Cannady SB;Comhair SA;Erzurum SC
气道上皮细胞中一氧化氮合酶2（NOS 2）的调节在先天宿主对多种微生物因子的应答中起关键作用，并且还参与病理性气道炎症的产生。在指导NOS 2基因表达的重要信号级联中，有核因子κB（NFκB）和干扰素-γ（IFNγ）/信号转导和转录激活因子1（STAT-1）。以往的研究表明激活蛋白-1（AP-1），特别是AP-1的c-Fos组分，影响NOS 2的表达。我们研究了使用RNA干扰siRNA调节c-Fos对NOS 2基因表达的影响。用稳定转染过表达c-Fos siRNA的质粒（FOSi）转染A549细胞，可使IFN γ诱导的NOS 2蛋白表达减少。相比之下，经典的IFN γ诱导的信号转导途径干扰素调节因子-1（IRF-1）和pSTAT-1在FOSi和对照细胞中以相似的幅度被激活。DNA-蛋白质结合分析表明，c-Fos结合存在于野生型细胞中，但在FOSi克隆中减少。DNA-蛋白质结合试验可检测到FOSi克隆的NFκB活化，这可能有助于NOS 2表达的降低。总之，这些研究表明，c-Fos是诱导型NOS 2表达的必要和特异性组分。
The regulation of nitric oxide synthase 2 (NOS2) in airway epithelial cells plays a key role in the innate host response to a wide variety of microbial agents and also participates in the generation of pathologic airway inflammation. Among the important signalling cascades that direct NOS2 gene expression are nuclear factor κB (NFκB) and interferon-γ (IFNγ)/signal transducer and activator of transcription 1 (STAT-1). Previous studies suggest activator protein-1 (AP-1), in particular c-Fos component of AP-1, influences NOS2 expression. We investigated the effect of c-Fos modulation using RNA interference siRNA on NOS2 gene expression. A549 cells stably transfected with a plasmid overexpressing a c-Fos siRNA construct (FOSi) resulted in a decrease of NOS2 protein inducibility by IFN γ. In contrast, classical IFN γ inducible signal transduction pathways interferon regulated factor-1 (IRF-1) and pSTAT-1 were activated at a similar magnitude in FOSi and control cells. DNA–protein binding assays showed that c-Fos binding was present in wild type cells, but reduced in FOSi clones. FOSi clones had activation of NFκB detectable by DNA–protein binding assays, which may have contributed to a decrease of NOS2 expression. Overall, these studies indicate that c-Fos is a requisite and specific component for inducible NOS2 expression.
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DOI：
10.1165/rcmb.2006-0329sm
发表时间：
2007-06-01
影响因子：
6.4
作者：
Ckless, Karina;van der Vliet, Albert;Janssen-Heininger, Yvonne
通讯作者：
Janssen-Heininger, Yvonne
影响因子：
15.9
作者：
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Erzurum, SC
影响因子：
56.9
作者：
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CURRAN, T
影响因子：
4.8
作者：
Marks-Konczalik, J;Chu, SC;Moss, J
通讯作者：
Moss, J
影响因子：
56.9
作者：
Brummelkamp, TR;Bernards, R;Agami, R
通讯作者：
Agami, R