Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. TRIM59 has been showed to participate in many pathological processes, such as inflammation, cytotoxicity and tumorigenesis. However, the molecular mechanisms controlling its expression in activated macrophages are not fully understood. Here we report that TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages. TRIM59 is highly expressed in macrophages, and markedly decreased by LPS stimuli in vivo and in vitro. TRIM59 promoter activity is also significantly suppressed by LPS and further analysis demonstrated that Sp1 and Nrf1 directly bound to the proximal promoter of TRIM59 gene. LPS treatment significantly decreased Sp1 expression, nuclear translocation and reduced its binding to the promoter, whereas increased Nrf1 expression, nuclear translocation and enhanced its binding to the promoter. Moreover, LPS-decreased TRIM59 expression was reversed by JNK inhibitor. Finally, TRIM59 level is significantly decreased during atherosclerosis progression. Taken together, our results demonstrated that TRIM59 expression was precisely regulated by Sp1 and Nrf1 in LPS-activated macrophages, which may be dependent on the activation of JNK signaling pathway and TRIM59 may be a potential therapeutic target for inflammatory diseases such as atherosclerosis.

中文翻译：

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TRIM59的表达受LPS激活的巨噬细胞通过JNK信号通路的Sp1和Nrf1调控。

活化的巨噬细胞在许多炎性疾病（包括败血性休克和动脉粥样硬化）中起重要作用。已经显示TRIM59参与许多病理过程，例如炎症，细胞毒性和肿瘤发生。但是，尚不完全了解控制其在活化的巨噬细胞中表达的分子机制。在这里我们报告TRIM59表达受LPS激活的巨噬细胞中的Sp1和Nrf1的调节。TRIM59在巨噬细胞中高表达，并在体内和体外被LPS刺激显着降低。LPS还显着抑制了TRIM59启动子的活性，进一步分析表明Sp1和Nrf1直接与TRIM59基因的近端启动子结合。LPS处理可显着降低Sp1表达，核易位并降低其与启动子的结合，而增加Nrf1表达，核易位并增强其与启动子的结合。此外，JNK抑制剂逆转了LPS降低的TRIM59表达。最后，在动脉粥样硬化进展期间，TRIM59水平显着降低。两者合计，我们的结果表明，在LPS激活的巨噬细胞中，Sp1和Nrf1精确调节了TRIM59的表达，这可能取决于JNK信号通路的激活，而TRIM59可能是炎性疾病（如动脉粥样硬化）的潜在治疗靶标。