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

Ling Liu, Yuekui Li, Linda J. Van Eldik, W. Sue T. Griffin, Steven W. Barger

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)546-553
Number of pages8
JournalJournal of Neurochemistry
Volume92
Issue number3
DOIs
StatePublished - Feb 2005

Keywords

  • Alzheimer's disease
  • Down's syndrome
  • Gene regulation
  • Microglia
  • NFκB
  • Sp1

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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