Amyloid-β peptides induce cell proliferation and macrophage colony-stimulating factor expression via the PI3-kinase/Akt pathway in cultured Ra2 microglial cells

Sachiko Ito, Makoto Sawada, Masataka Haneda, Satoshi Fujii, Kentaro Oh-Hashi, Kazutoshi Kiuchi, Masahide Takahashi, Ken Ichi Isobe

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Alzheimer's disease is characterized by numerous amyloid-β peptide (Aβ) plaques surrounded by microglia. Here we report that Aβ induces the proliferation of the mouse microglial cell line Ra2 by increasing the expression of macrophage colony-stimulating factor (M-CSF). We examined signal cascades for Aβ-induced M-CSF mRNA expression. The induction of M-CSF was blocked by a phosphatidylinositol 3 kinase (PI3-kinase) inhibitor (LY294002), a Src family tyrosine kinase inhibitor (PP1) and an Akt inhibitor. Electrophoretic mobility shift assays showed that Aβ enhanced NF-κB binding activity to the NF-κB site of the mouse M-CSF promoter, which was blocked by LY294002. These results indicate that Aβ induces M-CSF mRNA expression via the PI3-kinase/Akt/NF-κB pathway.

Original languageEnglish
Pages (from-to)1995-2000
Number of pages6
JournalFEBS Letters
Volume579
Issue number9
DOIs
Publication statusPublished - 28-03-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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