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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype.
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Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype.

机译：硫酸软骨素二糖刺激小胶质细胞采取新的调节表型。

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A disaccharide degradation product of chondrotin sulfate proteoglycan-disaccharide (CSPG-DS) has been implicated previously in the inhibition of neurodegeneration by influencing microglia activation. In this study, genome-wide microarray analysis was used to identify specific gene expression profiles of CSPG-DS-stimulated BV-2 microglia-like cells. Gene products involved in phagocytosis, detoxification, migration, immune regulation, and antigen presentation were found to be altered significantly. These findings were replicated and compared with IFN-gamma-stimulated primary microglia using real-time quantitative RT-PCR validation. Importantly, a unique transcriptional phenotype with anti-inflammatory and IFN-gamma counter-regulatory properties partially related to alternatively activated macrophages was identified. Using functional cell assays, we found that CSPG-DS-stimulated microglia possess increased phagocytic capacity but lack direct cytotoxic effects such as secretion of NO. Furthermore, conditioned media from CSPG-DS-treated microglia did not diminish the viability or cause apoptosis of cultured photoreceptor cells and partially rescued these cells from IFN-gamma-induced apoptosis. Taken together, our data provide a unique transcript dataset and important in vitro findings about the functional properties of CSPG-DS-activated microglia. These might be starting points to explore the in vivo role of CSPG-DS as a bioactive microglia regulator and its potential, therapeutic application in immune-related, neurodegenerative disorders.
机译：硫酸软骨素蛋白聚糖-二糖（CSPG-DS）的二糖降解产物先前已涉及通过影响小胶质细胞活化来抑制神经变性。在这项研究中，全基因组微阵列分析用于鉴定CSPG-DS刺激的BV-2小胶质细胞样细胞的特定基因表达谱。发现与吞噬作用，排毒，迁移，免疫调节和抗原呈递有关的基因产物发生了显着变化。复制这些发现，并使用实时定量RT-PCR验证与IFN-γ刺激的原发性小胶质细胞进行比较。重要的是，鉴定出具有与选择性激活的巨噬细胞部分相关的抗炎和IFN-γ反调节特性的独特转录表型。使用功能细胞分析，我们发现CSPG-DS刺激的小胶质细胞具有增加的吞噬能力，​​但缺乏直接的细胞毒作用，例如NO的分泌。此外，来自CSPG-DS处理的小胶质细胞的条件培养基不会降低培养的感光细胞的活力或引起其凋亡，并且不会从IFN-γ诱导的凋亡中部分拯救这些细胞。两者合计，我们的数据提供了一个独特的成绩单数据集和有关CSPG-DS激活的小胶质细胞功能特性的重要体外发现。这些可能是探索CSPG-DS在体内作为生物活性小胶质细胞调节剂的作用及其在免疫相关的神经退行性疾病中的潜在治疗应用的起点。

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