CCAAT/enhancer binding protein delta in microglial activation

• Published in: Journal of neuroscience research 2010-04, Vol.88 (5), p.1113-1123
• Main Authors: Ejarque-Ortiz, Aroa, Gresa-Arribas, Núria, Straccia, Marco, Mancera, Pilar, Solà, Carme, Tusell, Josep Maria, Serratosa, Joan, Saura, Josep
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Astrocytes - drug effects; Astrocytes - immunology; Astrocytes - metabolism; Binding Sites - physiology; CCAAT-Enhancer-Binding Protein-beta - metabolism; CCAAT-Enhancer-Binding Protein-delta - genetics; CCAAT-Enhancer-Binding Protein-delta - metabolism; Cells, Cultured; Coculture Techniques; Cyclooxygenase 2 - genetics; Dose-Response Relationship, Drug; Encephalitis - genetics; Encephalitis - immunology; Encephalitis - metabolism; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation - physiology; Glial activation; Gliosis - immunology; Gliosis - metabolism; Gliosis - physiopathology; Inflammation Mediators - pharmacology; lipopolysaccharide; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred C57BL; microglia; Microglia - drug effects; Microglia - immunology; Microglia - metabolism; Promoter Regions, Genetic - physiology; RNA, Messenger - drug effects; RNA, Messenger - metabolism; toll-like receptors; Toll-Like Receptors - agonists; Toll-Like Receptors - metabolism; transcription factors; Transcriptional Activation - physiology; Up-Regulation - genetics
• ISSN: 0360-4012; 1097-4547; 1097-4547
• DOI: 10.1002/jnr.22272

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.