Bioluminescence imaging of the brain response to acute inflammation in living C/EBP reporter mice

The transcription factor CCAAT enhancer binding protein (C/EBP) is a key regulator of inflammation and immune responses, and recent studies suggest it is involved in inflammatory processes in the nervous system. We generated a transgenic reporter mouse model, carrying the luciferase (luc) gene under the transcriptional control of C/EBP, for visualising C/EBP activity in vivo. Real-time bioluminescence imaging reflecting C/EBP activity was performed in an acute inflammation model, after systemic administration of lipopolysaccharides (LPS), in C/EBP-luc mice. A striking activity of C/EBP was imaged predominantly in the brain of living C/EBP-luc mice in response to LPS, showing for the first time in vivo that C/EBP mediates the brain response to inflammation. Furthermore, dexamethasone, a potent anti-inflammatory agent, diminished the LPS-induced C/EBP activity demonstrating the physiological regulation of bioluminescence intensity in the brain of C/EBP-luc mice. Our results implicate that C/EBP reporter mice have the potential to be a valuable tool for studies on the mechanisms of brain inflammation in vivo and for the noninvasive preclinical evaluation of therapeutic agents targeting neuroinflammatory diseases. (C) 2011 Elsevier Ireland Ltd. All rights reserved.