Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
Neuroscience. 2013 Apr 3;235:141-8. doi: 10.1016/j.neuroscience.2012.12.030. Epub 2013 Jan 18.
Fibroblast growth loop (FGL) is a neural cell adhesion molecule (NCAM)-mimetic peptide that mimics the interaction of NCAM with fibroblast growth factor receptor (FGFR). FGL increases neurite outgrowth and promotes neuronal survival in vitro, and it has also been shown to have neuroprotective effects in vivo. More recent evidence has indicated that FGL has anti-inflammatory effects, decreasing age-related changes in microglial activation and production of inflammatory cytokines. These changes have been associated with an FGL-induced increase in expression of the glycoprotein, CD200, which interacts with its receptor to help maintain microglia in a quiescent state. However whether the FGL-induced anti-inflammatory effects are CD200-dependent has not been examined. The objective of this study was to address this question. Mixed glia were prepared from brain tissue of neonatal wildtype and CD200-deficient mice and preincubated with FGL prior to stimulation with lipopolysaccharide (LPS). Cells were assessed for mRNA expression of markers of microglial activation, CD11b, CD40 and intercellular adhesion molecule 1 (ICAM-1) and also the inflammatory cytokines, interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, while supernatant concentrations of these cytokine were also assessed. LPS significantly increased all these parameters and the effect was greater in cells prepared from CD200-deficient mice. Whereas FGL attenuated the LPS-induced changes in cells from wildtype mice, it did not do so in cells from CD200-deficient mice. We conclude that the FGL-induced changes in microglial activation are CD200-dependent and demonstrate that the interaction of astrocytes with microglia is critically important for modulating microglial activation.
成纤维细胞生长环（FGL）是一种神经细胞黏附分子（NCAM）模拟肽，模拟 NCAM 与成纤维细胞生长因子受体（FGFR）的相互作用。FGL 可增加体外神经突生长并促进神经元存活，并且已显示在体内具有神经保护作用。最近的证据表明，FGL 具有抗炎作用，可减少小胶质细胞活化和炎性细胞因子产生的与年龄相关的变化。这些变化与 FGL 诱导的糖蛋白 CD200 的表达增加有关，CD200 与其受体相互作用有助于维持小胶质细胞处于静止状态。然而，FGL 诱导的抗炎作用是否依赖于 CD200 尚未得到检验。本研究的目的是解决这个问题。从新生野生型和 CD200 缺陷型小鼠的脑组织中制备混合神经胶质细胞，并在用脂多糖（LPS）刺激之前用 FGL 进行预孵育。评估细胞 CD11b、CD40 和细胞间黏附分子 1（ICAM-1）的小胶质细胞活化标志物以及炎性细胞因子白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α的 mRNA 表达，同时还评估了这些细胞因子的上清液浓度。LPS 显著增加了所有这些参数，并且在 CD200 缺陷型小鼠制备的细胞中作用更大。虽然 FGL 减弱了野生型小鼠细胞中 LPS 诱导的变化，但在 CD200 缺陷型小鼠细胞中却没有。我们得出结论，FGL 诱导的小胶质细胞活化变化依赖于 CD200，并且表明星形胶质细胞与小胶质细胞的相互作用对于调节小胶质细胞活化至关重要。
