title: Bioluminescence imaging of the brain response to acute inflammation in living C/EBP reporter mice.
abstract: 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.
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, 4 Newark Street, Whitechapel, London E12AT, UK.
authors.forename: Luis
authors.initials: L
authors.lastname: Lopez de Heredia
authors.forename: Archana
authors.initials: A
authors.lastname: Gengatharan
authors.forename: Julie
authors.initials: J
authors.lastname: Foster
authors.forename: Stephen
authors.initials: S
authors.lastname: Mather
authors.forename: Charalambos
authors.initials: C
authors.lastname: Magoulas
mesh_terms: D000208:Acute Disease; D000818:Animals; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter / Q000235:genetics*; D018836:Inflammation Mediators / Q000502:physiology* / Q000627:therapeutic use; D008156:Luciferases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011247:Pregnancy
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D018836:Inflammation Mediators; D008164:Luminescent Proteins; D008156:Luciferases