Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, PR China.
Department of Neurosurgery, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, PR China.
Biochem Biophys Res Commun. 2018 Jul 12;502(2):269-275. doi: 10.1016/j.bbrc.2018.05.159. Epub 2018 May 26.
Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia, the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.
神经炎症在神经退行性疾病的发生过程中起着关键作用，在此过程中，小胶质细胞被激活并产生促炎介质。Yin-Yang1（YY1）是一种多功能转录因子，广泛表达于免疫系统的细胞中，并参与多种细胞过程。然而，YY1 是否参与神经炎症过程尚不清楚。在本研究中，我们发现 YY1 在脂多糖（LPS）刺激的 BV2 小胶质细胞中逐渐上调，这依赖于核因子 kappa B（NF-κB）的转录激活功能。此外，YY1 敲低显著抑制 LPS 诱导的 BV-2 细胞中 NF-κB 信号和白细胞介素-6（IL-6）的表达，但不抑制丝裂原活化蛋白激酶（MAPK）信号。此外，YY1 通过与 p65 相互作用增强 p65 与 IL-6 启动子的结合，但降低 IL-6 启动子上 H3K27ac 的修饰，最终增加 IL-6 的转录。综上所述，这些结果首次揭示了 YY1 在神经炎症反应中对 IL-6 表达的调控机制，为神经炎症研究提供了新的思路。
