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Polarized microglia do not influence oligodendrocyte lineage cells via astrocytes

机译:偏振微胶质细胞不会通过星形胶质细胞影响oligodendrocyte谱系细胞

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Microglia can adopt different activation patterns, ranging from a pro-inflammatory M1- to an anti-inflammatory M2-like phenotype in which they play crucial roles in various neuroinflammatory diseases. M2-like microglia are described to drive remyelination, whereas detrimental effects have been attributed to M1-like microglia. How polarized microglia might act on oligodendrocyte lineage cells indirectly by influencing astrocytes has not been studied in detail. In this study, conditioned media from polarized murine microglia were used to treat astrocytes and astrocytic gene expression was analyzed by microarray for genes known to influence oligodendrocyte lineage cells. Supernatants of astrocytes previously stimulated with soluble effectors from polarized microglia were used to investigate effects on oligodendrocyte precursor cells (OPC). Growth factors known to induce OPC proliferation, differentiation, and survival were upregulated in astrocytes treated with supernatants from M1-like microglia while MO- and M2-like microglia only had negligible effects on the expression of these factors in astrocytes. Despite the upregulation of these factors in M1 stimulated astrocytes there were no significant effects on OPC in vitro. All astrocyte supernatants induced proliferation of A2B5(+) OPC and inhibited differentiation of OPC into mature oligodendrocytes. A trend toward enhanced migration of OPC was induced by M1 stimulated astrocytes. Our data suggest that M1-like microglia may potentially influence OPC and remyelination indirectly via astrocytes by inducing the expression of respective growth factors, however, this has no significant effect in addition to the already strong effects of unstimulated astrocytes on OPC. Nevertheless, the observed effect may be of relevance in other pathophysiological scenarios.
机译:微胶质细胞可以采用不同的激活模式,从促炎M1-到抗炎M2样表型,其中它们在各种神经炎疾病中起着至关重要的作用。描述了M2样的微胶质细胞以驱动重新髓鞘,而不利影响已归因于M1样MICROGLIA。偏振的微胶质细胞如何通过影响星形胶质细胞间接地对寡突胶质细胞谱系细胞作用的方式,尚未详细研究。在该研究中,使用来自偏振鼠微胶质细胞的条件培养基来治疗星形胶质细胞,通过微阵列分析了用于影响少偶突细胞谱系细胞的基因的微阵列。使用来自偏振微胶质的可溶性效应刺激的星形胶质细胞的上清液研究了对少突胶质细胞前体细胞(OPC)的影响。已知诱导OPC增殖,分化和存活的生长因子在用M1样MICROGLIA的上清液处理的星形胶质细胞中上调,而MO-and M2样的小胶质细胞仅对星形胶质细胞的这些因子表达可忽略不计。尽管M1刺激的星形胶质细胞对这些因素的上调,但在体外对OPC没有显着影响。所有星形胶质细胞上清液诱导A2B5(+)OPC的增殖,并抑制OPC分化为成熟的少偶突胶质细胞。 M1刺激的星形胶质细胞诱导了对OPC迁移增强的趋势。我们的数据表明,M1样MICROGLIA可能通过诱导各自生长因子的表达来间接地通过星形胶质细胞间接地影响OPC和重新髓鞘,但除了未刺激的星形胶质细胞对OPC上的已经强烈效应,这对这无显着影响。然而,观察到的效果可能与其他病理生理情景相关。

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