S100β Induction of the Proinflammatory Cytokine Interleukin‐6 in Neurons

• Published in: Journal of neurochemistry 2000-01, Vol.74 (1), p.143-150
• Main Authors: Yuekui, Li, Barger, Steven W., Liu, Ling, Mrak, Robert E., Griffin, W. Sue T.
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Interleukin‐6; Medical sciences; Neurology; Neuronal culture; Nuclear factor κB; S100^b protein; S100b protein; S100β
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.0740143.x

: 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.