C/EBPβ expression in activated microglia in amyotrophic lateral sclerosis

NEUROBIOLOGY OF AGING

卷:33

Article

Valente, Tony¹  Mancera, Pilar²  Tusell, Josep M.²  Serratosa, Joan²  Saura, Josep¹ 

[1] Univ Barcelona, IDIBAPS, Sch Med, Biochem & Mol Biol Unit, E-08036 Barcelona, Spain

[2] CSIC, IDIBAPS, Dept Cerebral Ischemia & Neurodegenerat, Inst Invest Biomed Barcelona, Barcelona, Spain

关键词: Neuroinflammation;    Microglia;    Astrocyte C/EBP beta;    Amyotrophic lateral sclerosis;    NOS2;    COX-2;    IL-1 beta;    IL-6;    TNF alpha;    Lipopolysaccharide;   

DOI  :  10.1016/j.neurobiolaging.2011.09.019

来源: Elsevier

【 摘 要 】

Neuroinflammation is thought to play a pathogenic role in many neurodegenerative disorders including amyotrophic lateral sclerosis (ALS). In this study we demonstrate that the expression of nitric oxide (NO) synthase-2 (NOS2), and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) with interferon-gamma is higher in microglial-enriched cultures from G93A-SOD1 mice, an ALS animal model, than from wild type mice. The levels of CCAAT/enhancer binding protein beta (C/EBP beta), a transcription factor that regulates proinflammatory gene expression, are also upregulated in activated G93A-SOD1 microglial cells. In vivo, systemic lipopolysaccharide also induces an exacerbated neuroinflammatory response in G93A-SOD1 mice versus wild type mice, with increased expression of glial fibrillary acidic protein (GFAP), CD11b, nitric oxide synthase-2, cyclooxygenase-2, proinflammatory cytokines, and C/EBP beta. Finally, we report that C/EBP beta is expressed by microglia in the spinal cord of ALS patients. This is the first demonstration to our knowledge of microglial C/EBP beta expression in human disease. Altogether these findings indicate that G93A-SOD1 expression results in an exacerbated pattern of neuroinflammation and suggest that C/EBP beta is a candidate to regulate the expression of potentially neurotoxic genes in microglial cells in ALS. (C) 2012 Elsevier Inc. All rights reserved.

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