MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-κB and PI3K-Akt pathways

J Cell Physiol. 2018 Jan;234(1):904-914. doi: 10.1002/jcp.26918. Epub 2018 Aug 4.

Abstract

Recent evidence have suggested that neuroinflammation and ischemia induce the activation of two different types of reactive astrocytes, termed A1 and A2. Additionally, A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative diseases, such as Alzheimer's disease (AD). In the current study, we constructed an Aβ42-activated microglia-conditioned medium to induce A1 astrocytic activation via secretion of interleukin 1α, tumor necrosis factor, and complement component 1q in vitro, and indicated the regulatory role of milk fat globule epidermal growth factor 8 (MFG-E8) on A1/A2 astrocytic alteration through the downregulation of nuclear factor-κB and the upregulation of PI3K-Akt. This study showed that MFG-E8 suppressed A1 astrocytes and holds great potential for the treatment of AD.

Keywords: Alzheimer’s disease; Aβ42; MFG-E8; astrocyte; microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / genetics
  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Complement C1q / genetics
  • Culture Media, Conditioned / pharmacology
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Inflammation / therapy
  • Interleukin-1alpha / genetics
  • Mice
  • Microglia / metabolism
  • Microglia / pathology
  • Milk Proteins / genetics
  • Milk Proteins / pharmacology*
  • NF-kappa B / genetics
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • Peptide Fragments / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Amyloid beta-Peptides
  • Antigens, Surface
  • Culture Media, Conditioned
  • Interleukin-1alpha
  • Mfge8 protein, mouse
  • Milk Proteins
  • NF-kappa B
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • amyloid beta-protein (1-42)
  • Complement C1q
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt