Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid beta in differentiated SH-SY5Y cells

Neurobiol Aging. 2017 Dec:60:173-182. doi: 10.1016/j.neurobiolaging.2017.08.022. Epub 2017 Sep 1.

Abstract

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.

Keywords: Alzheimer's disease; Amyloid beta oligomers; Anti-inflammatory; Cell-to-cell transfer; Cytokine; Proinflammatory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Cell Line
  • Endosomes / metabolism
  • Humans
  • Interleukin-10 / physiology
  • Interleukin-13 / physiology
  • Interleukin-4 / physiology
  • Lysosomes / metabolism
  • Macrophages / physiology*
  • Microglia / physiology*
  • Protein Transport
  • Recombinant Proteins

Substances

  • Amyloid beta-Peptides
  • IL10 protein, human
  • IL4 protein, human
  • Interleukin-13
  • Recombinant Proteins
  • Interleukin-10
  • Interleukin-4