Microglia responses to pro-inflammatory stimuli (LPS, IFNγ+TNFα) and reprogramming by resolving cytokines (IL-4, IL-10)

Microglia respond to CNS injuries and diseases with complex reactions, often called “activation.” A pro-inflammatory phenotype (also called classical or M1 activation) lies at one extreme of the reactivity spectrum. There were several motivations for this study. First, bacterial endotoxin (lipopolysaccharide, LPS) is the most commonly used pro-inflammatory stimulus for microglia, both in vitro and in vivo; however, pro-inflammatory cytokines (e.g., IFNγ, TNFα) rather than LPS will be encountered with sterile CNS damage and disease. We lack direct comparisons of responses between LPS and such cytokines. Second, while transcriptional profiling is providing substantial data on microglial responses to LPS, these studies mainly use mouse cells and models, and there is increasing evidence that responses of rat microglia can differ. Third, the cytokine milieu is dynamic after acute CNS damage, and an important question in microglial biology is: How malleable are their responses? There are very...

小胶质细胞（Microglia）对中枢神经系统（Central Nervous System, CNS）损伤和疾病会产生复杂反应，通常被称为“激活”。促炎表型（也称为经典激活或M1激活）位于反应谱的一个极端。本研究有几个动机：首先，细菌内毒素——脂多糖（lipopolysaccharide, LPS）是体外和体内研究中最常用的小胶质细胞促炎刺激物；然而，在无菌性中枢神经系统损伤和疾病中，遇到的是促炎细胞因子（如干扰素γ、肿瘤坏死因子α）而非LPS，我们缺乏对LPS与这类细胞因子反应的直接比较。其次，尽管转录谱分析已提供大量关于小胶质细胞对LPS反应的数据，但这些研究主要使用小鼠细胞和模型，且越来越多的证据表明大鼠小胶质细胞的反应可能存在差异。第三，急性中枢神经系统损伤后细胞因子微环境呈动态变化，小胶质细胞生物学中的一个重要问题是：它们的反应具有多大的可塑性？目前关于...