Molecular and Cellular Neuroscience Department, The Scripps Research Institute La Jolla, CA, USA.
Department of Biology, University of Wisconsin-Stevens Point Stevens Point, WI, USA.
Front Cell Neurosci. 2014 Aug 14;8:234. doi: 10.3389/fncel.2014.00234. eCollection 2014.
Emerging research has identified that neuroimmune factors are produced by cells of the central nervous system (CNS) and play critical roles as regulators of CNS function, directors of neurodevelopment and responders to pathological processes. A wide range of neuroimmune factors are produced by CNS cells, primarily the glial cells, but the role of specific neuroimmune factors and their glial cell sources in CNS biology and pathology have yet to be fully elucidated. We have used transgenic mice that express elevated levels of a specific neuroimmune factor, the cytokine IL-6 or the chemokine CCL2, through genetic modification of astrocyte expression to identify targets of astrocyte produced IL-6 or CCL2 at the protein level. We found that in non-transgenic mice constitutive expression of IL-6 and CCL2 occurs in the two CNS regions studied, the hippocampus and cerebellum, as measured by ELISA. In the CCL2 transgenic mice elevated levels of CCL2 were evident in the hippocampus and cerebellum, whereas in the IL-6 transgenic mice, elevated levels of IL-6 were only evident in the cerebellum. Western blot analysis of the cellular and synaptic proteins in the hippocampus and cerebellum of the transgenic mice showed that the elevated levels of CCL2 or IL-6 resulted in alterations in the levels of specific proteins and that these actions differed for the two neuroimmune factors and for the two brain regions. These results are consistent with cell specific profiles of action for IL-6 and CCL2, actions that may be an important aspect of their respective roles in CNS physiology and pathophysiology.
新兴研究已经确定，神经免疫因子由中枢神经系统（CNS）的细胞产生，并作为 CNS 功能的调节剂、神经发育的指导者以及对病理过程的反应者发挥关键作用。中枢神经系统细胞，主要是神经胶质细胞，会产生多种神经免疫因子，但特定神经免疫因子及其神经胶质细胞来源在中枢神经系统生物学和病理学中的作用尚未完全阐明。我们利用通过对星形胶质细胞表达的基因修饰，使特定神经免疫因子（细胞因子 IL-6 或趋化因子 CCL2）的表达水平升高的转基因小鼠，来鉴定星形胶质细胞产生的 IL-6 或 CCL2 在蛋白质水平上的作用靶点。我们发现，通过 ELISA 检测，在非转基因小鼠中，IL-6 和 CCL2 的组成型表达发生在研究的两个中枢神经系统区域，即海马体和小脑。在 CCL2 转基因小鼠中，海马体和小脑中的 CCL2 水平升高，而在 IL-6 转基因小鼠中，仅小脑中的 IL-6 水平升高。对转基因小鼠海马体和小脑中的细胞和突触蛋白进行 Western blot 分析表明，CCL2 或 IL-6 水平的升高导致特定蛋白水平发生变化，而这两种神经免疫因子和两个脑区的作用不同。这些结果与 IL-6 和 CCL2 的细胞特异性作用模式一致，这些作用可能是它们在中枢神经系统生理学和病理生理学中的各自作用的一个重要方面。
