Novel transcriptional regulation of the schlafen-2 gene in macrophages in response to TLR-triggered stimulation
Novel transcriptional regulation of the schlafen-2 gene in macrophages in response to TLR-triggered stimulation
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DOI：
10.1016/j.molimm.2007.03.001
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发表时间：
2007-07-01
影响因子：
3.6
通讯作者：
Kwon, Hyung-Joo
中科院分区：
文献类型：
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作者：
Sohn, Wern-Joo;Kim, Dongbum;Kwon, Hyung-Joo
Schlafen-2（slfn-2）是slfn家族的成员，是T细胞发育的调节因子，其表达在微生物病原体感染时发生改变。然而，slfn表达的分子机制尚不明确。在这项研究中，我们分离了slfn-2作为lps诱导的RAW 264.7细胞差异表达基因（DEGs），并检测了slfn-2在cpg - dna处理和lps处理的巨噬细胞中的表达和调控。我们在slfn-2基因中定义了一个转录起始位点。为了研究slfn-2基因的启动子组织，我们克隆了一个类似于转录起始位点上游1.8 kb的区域。序列分析显示AP-1和NF-kappa B的一致位点，综合突变分析、基于elisa的转录因子激活试验和ChIP试验表明，AP-1和NF-kappa B与启动子元件的功能相互作用是CpG-DNA和LPS处理巨噬细胞中toll样受体（TLR）介导的slfn-2基因表达所必需的。综上所述，我们首次鉴定出一个slfn-2启动子，并证明CpG-DNA和LPS通过激活巨噬细胞NF-kappa B和AP-1通路触发slfn-2基因表达。(c) 2007 Elsevier Ltd.版权所有。
Schlafen-2(slfn-2) is a member of slfn family, regulators of T cell development and its expression is altered during infection by microbial pathogens. However, the molecular mechanism involved in slfn expression is still to be determined. In this study, we isolated slfn-2 as a LPS-induced differentially expressed genes (DEGs) in RAW 264.7 cells and examined expression and regulation of slfn-2 in CpG-DNA-treated and LPS-treated macrophages. We defined a transcriptional start site in the slfn-2 gene. To examine the promoter organization of the slfn-2 gene, we cloned a similar to 1.8 kb region upstream of the transcription start site. Sequence analysis indicates consensus sites for AP-1 and NF-kappa B. Comprehensive mutant analyses, ELISA-based transcription factor activation assay, and ChIP assays reveal that functional interaction of AP-1 and NF-kappa B with the promoter element is necessary for the Toll-like receptor (TLR)-mediated slfn-2 gene expression by CpG-DNA and LPS treatment in macrophages. In summary, we identified a slfn-2 promoter for the first time and demonstrated that CpG-DNA and LPS triggers slfn-2 gene expression by activating NF-kappa B and AP-1 pathways in macrophages. (c) 2007 Elsevier Ltd. All rights reserved.