CCAAT/enhancer binding protein delta in microglial activation.
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.
Ejarque-Ortiz
Aroa
A
Department of Cerebral Ischaemia and Neurodegeneration, IIBB, CSIC, IDIBAPS, Barcelona, Spain.
Gresa-Arribas
Núria
N
Straccia
Marco
M
Mancera
Pilar
P
Solà
Carme
C
Tusell
Josep Maria
JM
Serratosa
Joan
J
Saura
Josep
J
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D005911:Gliosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics
D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D051743:CCAAT-Enhancer-Binding Protein-delta; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases