Abstract
The transcription factor CCAAT/enhancer binding protein delta (C/EBP delta) regulates transcription of genes that play important roles in glial activation. Previous studies have shown the astroglial expression of C/EBP delta but the microglial expression of C/EBP delta 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/EBP delta is expressed by microglia and it is upregulated in microglial activation. Lipopolysaccharide upregulates C/EBP delta 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/EBP delta 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/EBP delta from activated BV2 microglia binds to the cyclooxygenase-2 promoter and forms complexes with C/EBP beta isoforms. These results point to C/EBP delta as a putative key regulator of proinflammatory gene expression in microglial activation.
(c) 2009 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Astrocytes / drug effects
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Astrocytes / immunology
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Astrocytes / metabolism
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Binding Sites / physiology
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CCAAT-Enhancer-Binding Protein-beta / metabolism
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CCAAT-Enhancer-Binding Protein-delta / genetics*
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CCAAT-Enhancer-Binding Protein-delta / metabolism*
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Cells, Cultured
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Coculture Techniques
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Cyclooxygenase 2 / genetics
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Dose-Response Relationship, Drug
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Encephalitis / genetics*
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Encephalitis / immunology
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Encephalitis / metabolism*
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation / physiology
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Gliosis / immunology
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Gliosis / metabolism*
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Gliosis / physiopathology
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Inflammation Mediators / pharmacology
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Lipopolysaccharides / pharmacology
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Mice
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Mice, Inbred C57BL
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Microglia / drug effects
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Microglia / immunology
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Microglia / metabolism*
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Promoter Regions, Genetic / physiology
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Toll-Like Receptors / agonists
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Toll-Like Receptors / metabolism
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Transcriptional Activation / physiology
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Up-Regulation / genetics
Substances
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CCAAT-Enhancer-Binding Protein-beta
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Cebpb protein, mouse
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Inflammation Mediators
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Lipopolysaccharides
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RNA, Messenger
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Toll-Like Receptors
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CCAAT-Enhancer-Binding Protein-delta
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Cyclooxygenase 2
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Extracellular Signal-Regulated MAP Kinases