S100B-induced microglial and neuronal IL-1 expression is mediated by cell type-specific transcription factors

Both the astrocytic cytokine S100B and the pro-inflammatory interleukin-1 (IL-1) are elevated in Alzheimer's disease, and each has been implicated in Alzheimer-related neuropathology. We examined the gene-regulatory events through which S100B induces IL-1β expression. In primary microglia, S100B activated the transcription factors Sp1 and NFκB, followed by an increase in IL-1β mRNA levels. The latter was blocked by a peptide inhibitor of NFκB or by a double-stranded oligonucleotide containing a NFκB-binding site to serve as 'decoy' DNA and reduce available NFκB. But in primary cortical neurons, decoy and siRNA experiments indicated that the IL-1β induction by S100B was mediated by Sp1 without evidence of a role for NFκB. Our results suggest that the elevation of S100B and IL-1 in Alzheimer brain and consequent neurodegenerative events are mediated through cell-type specific gene-regulatory events, providing mechanistic insight into connections between glial activation and neuronal dysfunction.