ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Levels of the neurotrophic cytokine S100β and the proinflammatory cytokine interleukin-6 (IL-6) are both elevated in Alzheimer’s brain, and both have been implicated in β-amyloid plaque formation and progression. We used RT-PCR and electrophoretic mobility shift assay to assess S100β induction of IL-6 expression and the role of κB-dependent transcription in this induction in neuron-enriched cultures and in neuron-glia mixed cultures from fetal rat cortex. S100β (10 or 100 ng/ml × 24 h) increased IL-6 mRNA levels two- and fivefold, respectively (p 〈 0.05 in each case), and S100β (100-1,000 ng/ml) induced increases in medium levels of biologically active IL-6 (30-80%). Combined in situ hybridization and immunohistochemistry preparations localized IL-6 mRNA to neurons in these cultures. S100β induction of IL-6 expression correlated with an increase in DNA binding activity specific for a κB element and was inhibited (75%) by suppression of κB binding with double-stranded “decoy” oligonucleotides. The low levels of S100β required to induce IL-6 overexpression in neurons, shown here, suggest that overexpression of S100β induces neuronal expression of IL-6 and of IL-6-induced neurodegenerative cascades in Alzheimer’s disease.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0740143.x
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