Department of Cerebral Ischaemia and Neurodegeneration, IIBB, CSIC, IDIBAPS, Barcelona, Spain.
J Neurosci Res. 2010 Apr;88(5):1113-23. doi: 10.1002/jnr.22272.
The transcription factor CCAAT/enhancer binding protein delta (C/EBP delta) regulates transcription of genes that play important roles in glial activation. Previous studies have shown the astroglial expression of C/EBP delta but the microglial expression of C/EBP delta remains virtually unexplored, with the exception of two microarray studies. In this report, using murine primary cultures and BV2 cells we clearly demonstrate that C/EBP delta is expressed by microglia and it is upregulated in microglial activation. Lipopolysaccharide upregulates C/EBP delta both in microglia and in astrocytes. This effect is time-dependent, with a maximum effect at 3 hr at mRNA level and at 4-8 hr at protein level, and concentration-dependent, with a maximum effect at 100 ng/mL. The lipopolysaccharide-induced C/EBP delta upregulation in BV2 microglia is mimicked by agonists of the toll-like receptors 2, 3 and 9 and can be prevented by an inhibitor of extracellular signal-regulated kinase activation. C/EBP delta from activated BV2 microglia binds to the cyclooxygenase-2 promoter and forms complexes with C/EBP beta isoforms. These results point to C/EBP delta as a putative key regulator of proinflammatory gene expression in microglial activation.
转录因子 CCAAT/增强子结合蛋白 δ（C/EBP δ）调节在神经胶质细胞激活中发挥重要作用的基因的转录。先前的研究表明 C/EBP δ在星形胶质细胞中有表达，但 C/EBP δ在小神经胶质细胞中的表达实际上尚未得到探索，除了两项微阵列研究之外。在本报告中，使用鼠原代培养物和 BV2 细胞，我们清楚地表明 C/EBP δ由小神经胶质细胞表达，并在小神经胶质细胞激活时上调。脂多糖在小神经胶质细胞和星形胶质细胞中均可上调 C/EBP δ。这种效应是时间依赖性的，在 mRNA 水平上最大效应出现在 3 小时，在蛋白质水平上最大效应出现在 4-8 小时，并且呈浓度依赖性，在 100ng/ml 时最大效应。脂多糖诱导的 BV2 小神经胶质细胞中 C/EBP δ 的上调可被 Toll 样受体 2、3 和 9 的激动剂模拟，并可被细胞外信号调节激酶激活抑制剂所阻止。来自活化的 BV2 小神经胶质细胞的 C/EBP δ 与环加氧酶-2 启动子结合，并与 C/EBP β 同工型形成复合物。这些结果表明 C/EBP δ 是小胶质细胞激活中促炎基因表达的潜在关键调节因子。
