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Role of transcriptional factors Sp1, c-Rel, and c-Jun in LPS-induced C/EBP delta gene expression of mouse macrophages

机译:转录因子Sp1,c-Rel和c-Jun在LPS诱导的小鼠巨噬细胞C / EBPδ基因表达中的作用

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摘要

Transcription factor C/EBPs are involved in the regulation of various cellular responses. Here, it was suggested that C/EBP delta gene was activated by lipopolysaccharide (LPS) through transcription factors Sp1, c-Rel, and c-Jun. Assay of the luciferase reporter vectors containing a 5'-deletion of the C/EBP delta gene promoter indicated that a LPS-responsive element was positioned between -345 and -35 bp of mouse C/EBP delta gene promoter. Transcription factors Sp1, c-Rel, and c-Jun bound to this region were identified using both in vivo chromatin immunoprecipitation and in vitro DNA-protein binding assays. LPS enhanced the proteins and DNA binding capacities of c-Rel and c-Jun, and the downstream Sp1 site was essential for LPS-induced C/EBP delta gene. Treatment of cells with ERK/JNK/p38 inhibitors or NF-kappa B inhibitor inhibited the LPS-induced C/EBP delta gene expression by inhibiting c-Jun, c-Rel, and p300 binding to DNA. Our findings provide a better understanding of LPS-induced C/EBP delta gene expression.
机译:转录因子C / EBPs参与各种细胞反应的调节。在这里,暗示C / EBP delta基因被脂多糖(LPS)通过转录因子Sp1,c-Rel和c-Jun激活。包含C / EBPδ基因启动子5'缺失的荧光素酶报告载体的分析表明,LPS反应元件位于小鼠C / EBPδ基因启动子的-345和-35 bp之间。使用体内染色质免疫沉淀法和体外DNA-蛋白质结合测定法鉴定了与该区域结合的转录因子Sp1,c-Rel和c-Jun。 LPS增强了c-Rel和c-Jun的蛋白质和DNA结合能力,下游Sp1位点对于LPS诱导的C / EBP delta基因至关重要。用ERK / JNK / p38抑制剂或NF-κB抑制剂处理细胞可通过抑制c-Jun,c-Rel和p300与DNA的结合来抑制LPS诱导的C / EBP delta基因表达。我们的发现提供了对LPS诱导的C / EBPδ基因表达的更好理解。

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