Sackmann Valerie, Ansell Anna, Sackmann Christopher, Lund Harald, Harris Robert A, Hallbeck Martin, Nilsberth Camilla
Department of Clinical Pathology, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Centre for Molecular Medicine, Karolinska Hospital at Solna, Stockholm, Sweden.
Neurobiol Aging. 2017 Dec;60:173-182. doi: 10.1016/j.neurobiolaging.2017.08.022. Epub 2017 Sep 1.
Neuroinflammation plays an influential role in Alzheimer's disease (AD), although the mechanisms underlying this phenomenon remain largely unknown. Microglia are thought to be responsible for the majority of these effects and can be characterized into resting (M0), proinflammatory (M1), or anti-inflammatory (M2) functional phenotypes. We investigated the effects of conditioned macrophage media, as an analogue to microglia, on the transfer of oligomeric amyloid beta (oAβ) between differentiated SH-SY5Y cells. We also investigated how the different inflammatory environments related to intercellular and intracellular changes. We demonstrate that M2 products decrease interneuronal transfer of oAβ, while recombinant interleukin (IL)-4, IL-10, and IL-13 increase transfer. There were no alterations to the mRNA of a number of AD-related genes in response to the combination of oAβ and M0, M1, or M2, but several intracellular proteins, some relating to protein trafficking and the endosomal/lysosomal system, were altered. Stimulating microglia to an M2 phenotype may thus slow down the progression of AD and could be a target for future therapies.
神经炎症在阿尔茨海默病（AD）中起着重要作用，尽管这一现象背后的机制在很大程度上仍不清楚。小胶质细胞被认为是造成这些影响的主要原因，并且可以分为静息型（M0）、促炎型（M1）或抗炎型（M2）功能表型。我们研究了作为小胶质细胞类似物的条件巨噬细胞培养基对分化的SH-SY5Y细胞之间寡聚淀粉样β蛋白（oAβ）转移的影响。我们还研究了不同的炎症环境与细胞间和细胞内变化之间的关系。我们证明，M2产物可减少oAβ的神经元间转移，而重组白细胞介素（IL）-4、IL-10和IL-13则增加转移。oAβ与M0、M1或M2组合后，许多与AD相关基因的mRNA没有变化，但一些细胞内蛋白质发生了改变，其中一些与蛋白质运输和内体/溶酶体系统有关。因此，将小胶质细胞刺激为M2表型可能会减缓AD的进展，并且可能成为未来治疗的靶点。
