Microarray Analysis Supports a Role for CCAAT/Enhancer-binding Protein-β in Brain Injury

CCAAT/enhancer-binding protein-beta (C/EBPbeta) is a transcription factor that plays an important role in regulating cell growth and differentiation. This protein plays a central role in lymphocyte and adipocyte differentiation and hepatic regeneration and in the control of inflammation and immunity in the liver and in cells of the myelomonocytic lineage. Our previous studies suggested that this protein could also have important functions in the brain. Therefore, we were interested in the identification of downstream targets of this transcription factor in cells of neural origin. We performed cDNA microarray analysis and found that a total of 48 genes were up-regulated in C/EBPbeta-overexpressing neuronal cells. Of the genes that displayed significant changes in expression, several were involved in inflammatory processes and brain injury. Northern blot analysis confirmed the up-regulation of ornithine decarboxylase, 24p3/LCN2, GRO1/KC, spermidine/spermine N(1)-acetyltransferase, xanthine dehydrogenase, histidine decarboxylase, decorin, and TM4SF1/L6. Using promoter-luciferase reporter transfection assays, we showed the ornithine decarboxylase and 24p3 genes to be biological downstream targets of C/EBPbeta in neuroblastoma cells. Moreover, the levels of C/EBPbeta protein were significantly induced after neuronal injury, which was accompanied by increased levels of cyclooxygenase-2 enzyme. This strongly supports the concept that C/EBPbeta may play an important role in brain injury.