Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses.

Minshawi, Faisal, White, Mike RH, Muller, Werner, Humphreys, Neil, Jackson, Dean, Campbell, Barry J ORCID: 0000-0002-7407-012X, Adamson, Antony and Papoutsopoulou, Stamatia ORCID: 0000-0001-6665-8508
(2019) Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses. Scientific reports, 9 (1). 193-.

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Tumour necrosis factor (TNF) is a key cytokine during inflammatory responses and its dysregulation is detrimental in many inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Here, we used a bacterial artificial chromosome (BAC) construct that expresses luciferase under the control of the human TNF locus to generate a novel transgenic mouse, the hTNF.LucBAC strain. In vitro stimulation of hTNF.LucBAC cells of different origin revealed a cell specific response to stimuli demonstrating the integrated construct’s ability as a proxy for inflammatory gene response. Lipopolysaccharide was the most potent luciferase inducer in macrophages, while TNF was a strong activator in intestinal organoids. Lipopolysaccharide-induced luciferase activity in macrophages was downregulated by inhibitors of NF-κB pathway, as well as by Interleukin-10, a known anti-inflammatory cytokine. Moreover, the transgene-dependent luciferase activity showed a positive correlation to the endogenous murine soluble TNF secreted to the culture medium. In conclusion, the hTNF.LucBAC strain is a valuable tool for studying and screening molecules that target TNF synthesis and will allow further functional studies of the regulatory elements of the TNF locus.

Item Type: Article
Uncontrolled Keywords: Gene regulation, Inflammation
Depositing User: Symplectic Admin
Date Deposited: 31 Jan 2019 11:46
Last Modified: 19 Jan 2023 01:05
DOI: 10.1038/s41598-018-36969-x
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