beta-Amyloid and interleukin-1beta induce persistent NF-kappaB activation in rat primary glial cells

Int J Mol Med. 2005 Sep;16(3):449-53.

Abstract

An increasing body of evidence suggests that beta-amyloid (Abeta) and activated glial cells play a crucial part in the pathogenesis of Alzheimer's disease (AD). Activated glial cells surrounding the senile plaques, formed by Abeta peptides, have been proposed to promote neurodegeneration by producing putatively toxic factors, including the inflammatory cytokine interleukin-1beta (IL-1beta). Elevated levels of both IL-1beta and activated nuclear factor kappaB (NF-kappaB), a key transcription factor regulating a wide variety of inflammatory genes, have been found in the brains of AD patients. In this study, we have investigated the ability of the Abeta(25-35) peptide and IL-1beta, either alone or together, in activating NF-kappaB in glial cells. Mixed primary glial cells from rat were treated with IL-1beta and/or Abeta(25-35), and NF-kappaB binding activity was analyzed by electophoretic mobility shift assay. We observed that the induction of NF-kappaB binding activity induced by either IL-1beta or Abeta(25-35) showed a peak at 30 min, and significantly declined after 2 h. The induced NF-kappaB activation persisted after 24 h and even seemed to increase in cells treated with Abeta(25-35). The activation of NF-kappaB by Abeta(25-35) was shown to be dose-dependent. In addition, Abeta(25-35) potentiated the effect of IL-1beta in a dose-dependent manner when co-stimulating the cells. The potentiating effect of Abeta(25-35) on IL-1beta-induced NF-kappaB binding activity was observed after 30 min, 2 h and 24 h, and did not significantly differ over time. A possible explanation is that when glial cells are stimulated by inflammatory factors in the presence of Abeta peptides or senile plaques, the NF-kappaB negative feedback regulation is no longer functional.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Electrophoretic Mobility Shift Assay
  • Interleukin-1 / pharmacology*
  • NF-kappa B / metabolism*
  • Neuroglia / cytology
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Peptide Fragments / pharmacology*
  • Protein Binding / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Interleukin-1
  • NF-kappa B
  • Peptide Fragments
  • amyloid beta-protein (25-35)