Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6807071 | Neurobiology of Aging | 2013 | 15 Pages |
Abstract
The transcription factor CCAAT/enhancer binding protein δ (C/EBPδ) is expressed in activated astrocytes and microglia and can regulate the expression of potentially detrimental proinflammatory genes. The objective of this study was to determine the role of C/EBPδ in glial activation. To this end, glial activation was analyzed in primary glial cultures and in the central nervous system from wild type and C/EBPδâ/â mice. In vitro studies showed that the expression of proinflammatory genes nitric oxide (NO)synthase-2, cyclooxygenase-2, and interleukin (IL)-6 in glial cultures, and the neurotoxicity elicited by microglia in neuron-microglia cocultures, were decreased in the absence of C/EBPδ when cultures were treated with lipopolysaccharide (LPS) and interferon γ, but not with LPS alone. In C/EBPδâ/â mice, systemic LPS-induced brain expression of NO synthase-2, tumor necrosis factor-α, IL-1β, and IL-6 was attenuated. Finally, increased C/EBPδ nuclear expression was observed in microglial cells from amyotrophic lateral sclerosis patients and G93A-SOD1 mice spinal cord. These results demonstrate that C/EBPδ plays a key role in the regulation of proinflammatory gene expression in glial activation and suggest that C/EBPδ inhibition has potential for the treatment of neurodegenerative disorders, in particular, amyotrophic lateral sclerosis.
Keywords
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Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Tony Valente, Marco Straccia, Nuria Gresa-Arribas, Guido Dentesano, Josep M. Tusell, Joan Serratosa, Pilar Mancera, Carme Solà , Josep Saura,