β-Amyloid and interleukin-1β induce persistent NF-κB activation in rat primary glial cells
Stockholm University, Faculty of Science, Department of Neurochemistry2005 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 16, no 3, 449-453 p.Article in journal (Refereed) Published
An increasing body of evidence suggests that β-amyloid (Aβ) 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 Aβ peptides, have been proposed to promote neurodegeneration by producing putatively toxic factors, including the inflammatory cytokine interleukin-1β (IL-1β). Elevated levels of both IL-1β and activated nuclear factor κB (NF-κB), 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 Aβ(25-35) peptide and IL-1β, either alone or together, in activating NF-κB in glial cells. Mixed primary glial cells from rat were treated with IL-1β and/or Aβ(25-35), and NF-κB binding activity was analyzed by electophoretic mobility shift assay. We observed that the induction of NF-κB binding activity induced by either IL-1β or Aβ(25-35) showed a peak at 30 min, and significantly declined after 2 h. The induced NF-κB activation persisted after 24 h and even seemed to increase in cells treated with Aβ(25-35). The activation of NF-κB by Aβ(25-35) was shown to be dose-dependent. In addition, Aβ(25-35) potentiated the effect of IL-1β in a dose-dependent manner when co-stimulating the cells. The potentiating effect of Aβ(25-35) on IL-1β-induced NF-κB 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 Aβ peptides or senile plaques, the NF-κB negative feedback regulation is no longer functional.
Place, publisher, year, edition, pages
2005. Vol. 16, no 3, 449-453 p.
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-25297DOI: 10.3892/ijmm.16.3.449OAI: oai:DiVA.org:su-25297DiVA: diva2:199366