Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, People's Republic of China.
Inflammation. 2012 Aug;35(4):1558-66. doi: 10.1007/s10753-012-9471-4.
The heat shock transcription factor (HSF) is an important transactivator of the heat shock genes. Recent studies have shown that HSF1 acts as a repressor of non-heat shock genes to protect against endotoxemia. In this study, we found that heat shock treatment and HSF1 over-expression augmented the induction of interleukin (IL)-10 mRNA. Computational analysis of the mouse IL-10 promoter region showed that three potential heat shock elements (HSEs) were located at mouse IL-10 gene promoter, among which only the -387/-360 probe formed a complex with HSF1. The lack of binding of the other two HSEs to HSF1 suggested the critical role of the flanking sequences in the binding specificity of HSE to HSF1. Moreover, we showed that HSF1 overexpression transactivated mouse IL-10 gene promoter and this transcriptional activation was inhibited by the mutation of HSE in the -387/-360 region of IL-10 gene promoter using luciferase reporter assay. These findings indicate that HSF1 is a transcriptional activator of anti-inflammatory mediator IL-10 gene in RAW264.7 macrophages.
热休克转录因子(HSF)是热休克基因的重要转录激活子。最近的研究表明,HSF1 作为非热休克基因的抑制剂,可防止内毒素血症。在这项研究中,我们发现热休克处理和 HSF1 过表达增强了白细胞介素(IL)-10 mRNA 的诱导。对小鼠 IL-10 启动子区域的计算分析表明,三个潜在的热休克元件(HSE)位于小鼠 IL-10 基因启动子,其中只有 -387/-360 探针与 HSF1 形成复合物。其他两个 HSE 与 HSF1 结合的缺失表明侧翼序列在 HSE 与 HSF1 结合特异性中的关键作用。此外,我们还表明 HSF1 过表达可激活小鼠 IL-10 基因启动子,而使用荧光素酶报告基因检测,该转录激活可被 IL-10 基因启动子 -387/-360 区域 HSE 突变抑制。这些发现表明,HSF1 是 RAW264.7 巨噬细胞中抗炎介质 IL-10 基因的转录激活子。