CCAAT-enhancer binding protein-β expression and elevation in Alzheimer's disease and microglial cell cultures.
CCAAT-enhancer binding proteins are transcription factors that help to regulate a wide range of inflammatory mediators, as well as several key elements of energy metabolism. Because C/EBPs are expressed by rodent astrocytes and microglia, and because they are induced by pro-inflammatory cytokines that are chronically upregulated in the Alzheimer's disease (AD) cortex, we have investigated whether C/EBPs are expressed and upregulated in the AD cortex. Here, we demonstrate for the first time that C/EBPβ can be detected by Western blots in AD and nondemented elderly (ND) cortex, and that it is significantly increased in AD cortical samples. In situ, C/EBPβ localizes immunohistochemically to microglia. In microglia cultured from rapid autopsies of elderly patient's brains and in the BV-2 murine microglia cell line, we have shown that C/EBPβ can be upregulated by C/EBP-inducing cytokines or lipopolysaccharide and exhibits nuclear translocation possibly indicating functional activity. Given the known co-regulatory role of C/EBPs in pivotal inflammatory mechanisms, many of which are present in AD, we propose that upregulation of C/EBPs in the AD brain could be an important orchestrator of pathogenic changes.
Department of Biology, Northwest Nazarene University, Nampa, Idaho, United States of America.
Ron
R
Strohmeyer
Department of Biology, Northwest Nazarene University, Nampa, Idaho, United States of America.
Jadd
J
Shelton
Department of Biology, Northwest Nazarene University, Nampa, Idaho, United States of America.
Christopher
C
Lougheed
Department of Biology, Northwest Nazarene University, Nampa, Idaho, United States of America.
Trisia
T
Breitkopf
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus; D002478:Cells, Cultured; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
D016229:Amyloid beta-Peptides; D022782:CCAAT-Enhancer-Binding Protein-beta