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Whole-Body In Vivo Monitoring of Inflammatory Diseases Exploiting Human Interleukin 6-Luciferase Transgenic Mice.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2015 Oct; Vol. 35 (20), pp. 3590-601. Date of Electronic Publication: 2015 Aug 17. - Publication Year :
- 2015
-
Abstract
- Chronic inflammation underlies the pathological progression of various diseases, and thus many efforts have been made to quantitatively evaluate the inflammatory status of the diseases. In this study, we generated a highly sensitive inflammation-monitoring mouse system using a bacterial artificial chromosome (BAC) clone containing extended flanking sequences of the human interleukin 6 gene (hIL6) locus, in which the luciferase (Luc) reporter gene is integrated (hIL6-BAC-Luc). We successfully monitored lipopolysaccharide-induced systemic inflammation in various tissues of the hIL6-BAC-Luc mice using an in vivo bioluminescence imaging system. When two chronic inflammatory disease models, i.e., a genetic model of atopic dermatitis and a model of experimental autoimmune encephalomyelitis (EAE), were applied to the hIL6-BAC-Luc mice, luciferase bioluminescence was specifically detected in the atopic skin lesion and central nervous system, respectively. Moreover, the Luc activities correlated well with the disease severity. Nrf2 is a master transcription factor that regulates antioxidative and detoxification enzyme genes. Upon EAE induction, the Nrf2-deficient mice crossed with the hIL6-BAC-Luc mice exhibited enhanced neurological symptoms concomitantly with robust luciferase luminescence in the neuronal tissue. Thus, whole-body in vivo monitoring using the hIL6-BAC-Luc transgenic system (WIM-6 system) provides a new and powerful diagnostic tool for real-time in vivo monitoring of inflammatory status in multiple different disease models.<br /> (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Animals
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Brain immunology
Brain metabolism
Cells, Cultured
Dermatitis, Atopic drug therapy
Dermatitis, Atopic immunology
Dermatitis, Atopic metabolism
Dexamethasone pharmacology
Dexamethasone therapeutic use
Drug Evaluation, Preclinical
Encephalomyelitis, Autoimmune, Experimental immunology
Encephalomyelitis, Autoimmune, Experimental metabolism
Genes, Reporter
Humans
Interleukin-6 biosynthesis
Lipopolysaccharides pharmacology
Luciferases, Firefly biosynthesis
Luciferases, Firefly genetics
Macrophages immunology
Macrophages metabolism
Mice, Transgenic
NF-E2-Related Factor 2 genetics
NF-E2-Related Factor 2 metabolism
Organ Specificity
Sepsis immunology
Sepsis metabolism
Interleukin-6 genetics
Whole Body Imaging
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 35
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 26283726
- Full Text :
- https://doi.org/10.1128/MCB.00506-15