Ccaat/Enhancer Binding Protein-alpha is Down-regulated by Toll-like Receptor Agonists in Microglial Cells.
From: Department of Pharmacology and Toxicology, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
Journal of neuroscience research
- Publish Date: Apr 2007
- ISSN: 0360-4012
- Volume: 85
- Issue: 5
- Pages: 985-93
- Medium: Print
- Language: English
- Citation (JAMA): Ejarque-Ortiz Aroa, Tusell Josep M, Serratosa Joan, et al. Ccaat/Enhancer Binding Protein-alpha is Down-regulated by Toll-like Receptor Agonists in Microglial Cells.. J. Neurosci. Res. Apr 2007;85:985-93
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.
Mesh Headings (Keywords): Animals, Animals, Newborn, CCAAT-Enhancer-Binding Protein-alpha, Cells, Cultured, Coculture Techniques, Cytokines, Down-Regulation, Encephalitis, Gene Expression Regulation, Gliosis, Inflammation Mediators, Lipopolysaccharides, Mice, Mice, Inbred C57BL, Microglia, Oligonucleotides, Peptidoglycan, Poly I-C, RNA, Messenger, Toll-Like Receptors
Check for Full Text / PubMed Unique Identifier (PMID): 17253645
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