S100beta induction of the proinflammatory cytokine interleukin-6 in neurons.
Levels of the neurotrophic cytokine S100beta and the proinflammatory cytokine interleukin-6 (IL-6) are both elevated in Alzheimer's brain, and both have been implicated in beta-amyloid plaque formation and progression. We used RT-PCR and electrophoretic mobility shift assay to assess S100beta induction of IL-6 expression and the role of kappaB-dependent transcription in this induction in neuron-enriched cultures and in neuron-glia mixed cultures from fetal rat cortex. S100beta (10 or 100 ng/ml x 24 h) increased IL-6 mRNA levels two- and fivefold, respectively (p<0.05 in each case), and S100beta (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. S100beta induction of IL-6 expression correlated with an increase in DNA binding activity specific for a KB element and was inhibited (75%) by suppression of kappaB binding with double-stranded "decoy" oligonucleotides. The low levels of S100beta required to induce IL-6 overexpression in neurons, shown here, suggest that overexpression of S100beta induces neuronal expression of IL-6 and of IL-6-induced neurodegenerative cascades in Alzheimer's disease.
Li
Y
Y
Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, USA.
Barger
S W
SW
Liu
L
L
Mrak
R E
RE
Griffin
W S
WS
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000494:pharmacology*
D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D009418:S100 Proteins