title: CCAAT/enhancer binding protein-alpha is down-regulated by toll-like receptor agonists in microglial cells.
abstract: The transcription factor CCAAT/enhancer binding protein-alpha (C/EBPalpha) can regulate the expression of important genes in the inflammatory response, but little is known about its role in glial activation. By using primary cortical murine glial cultures, we show that C/EBPalpha is expressed by microglial cells in vitro. Lipopolysaccharide (LPS) down-regulates C/EBPalpha mRNA at 2 hr and all C/EBPalpha protein isoforms at 4 hr. This effect is elicited by LPS concentrations >/=100 pg/ml. LPS-induced C/EBPalpha down-regulation occurs in microglial cells both in mixed glial and in microglial-enriched cultures. As seen with LPS, other toll-like receptor agonists (polyinosinic-polycytidylic acid, peptidoglycan from Staphylococcus aureus, and the oligonucleotide CpG1668) also down-regulate C/EBPalpha whereas cytokines such as interleukin-1beta, interleukin-6, macrophage-colony stimulating factor, and interferon-gamma do not. These findings suggest that C/EBPalpha down-regulation in activated microglia could play an important role in the increased expression of genes that are potentially pathogenic in a variety of neurological disorders.
authors.affiliation: Department of Pharmacology and Toxicology, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
authors.forename: Aroa
authors.initials: A
authors.lastname: Ejarque-Ortiz
authors.forename: Josep M
authors.initials: JM
authors.lastname: Tusell
authors.forename: Joan
authors.initials: J
authors.lastname: Serratosa
authors.forename: Josep
authors.initials: J
authors.lastname: Saura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005911:Gliosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009841:Oligonucleotides / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists* / Q000378:metabolism*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009841:Oligonucleotides; D010457:Peptidoglycan; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D011070:Poly I-C