CCAAT/enhancer binding protein delta in microglial activation

Abstract

The transcription factor CCAAT/enhancer binding protein δ (C/EBPδ) regulates transcription of genes that play important roles in glial activation. Previous studies have shown the astroglial expression of C/EBPδ but the microglial expression of C/EBPδ remains virtually unexplored, with the exception of two microarray studies. In this report, using murine primary cultures and BV2 cells we clearly demonstrate that C/EBPδ is expressed by microglia and it is upregulated in microglial activation. Lipopolysaccharide upregulates C/EBPδ both in microglia and in astrocytes. This effect is time-dependent, with a maximum effect at 3 hr at mRNA level and at 4-8 hr at protein level, and concentration-dependent, with a maximum effect at 100 ng/mL. The lipopolysaccharide-induced C/EBPδ upregulation in BV2 microglia is mimicked by agonists of the toll-like receptors 2, 3 and 9 and can be prevented by an inhibitor of extracellular signal-regulated kinase activation. C/EBPδ from activated BV2 microglia binds to the cyclooxygenase-2 promoter and forms complexes with C/EBPβ isoforms. These results point to C/EBPδ as a putative key regulator of proinflammatory gene expression in microglial activation. © 2009 Wiley-Liss, Inc.