Human TNF-Luc reporter mouse: A new model to quantify inflammatory responsesCitation formats

  • External authors:
  • Faisal Minshawi
  • Michael White
  • Neil Humphreys
  • Barry J. Campbell
  • Stamatia Papoutsopoulou

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Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses. / Minshawi, Faisal; White, Michael; Muller, Werner; Humphreys, Neil; Jackson, Dean; Campbell, Barry J.; Adamson, Antony; Papoutsopoulou, Stamatia.

In: Scientific Reports, 2019.

Research output: Contribution to journalArticle

Harvard

APA

Minshawi, F., White, M., Muller, W., Humphreys, N., Jackson, D., Campbell, B. J., ... Papoutsopoulou, S. (2019). Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses. Scientific Reports. https://doi.org/10.1038/s41598-018-36969-x

Vancouver

Author

Minshawi, Faisal ; White, Michael ; Muller, Werner ; Humphreys, Neil ; Jackson, Dean ; Campbell, Barry J. ; Adamson, Antony ; Papoutsopoulou, Stamatia. / Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses. In: Scientific Reports. 2019.

Bibtex

@article{794f420ba80b4decbacc4655bdc7c533,
title = "Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses",
abstract = "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-B 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.",
author = "Faisal Minshawi and Michael White and Werner Muller and Neil Humphreys and Dean Jackson and Campbell, {Barry J.} and Antony Adamson and Stamatia Papoutsopoulou",
year = "2019",
doi = "10.1038/s41598-018-36969-x",
language = "English",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - Human TNF-Luc reporter mouse: A new model to quantify inflammatory responses

AU - Minshawi, Faisal

AU - White, Michael

AU - Muller, Werner

AU - Humphreys, Neil

AU - Jackson, Dean

AU - Campbell, Barry J.

AU - Adamson, Antony

AU - Papoutsopoulou, Stamatia

PY - 2019

Y1 - 2019

N2 - 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-B 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.

AB - 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-B 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.

U2 - 10.1038/s41598-018-36969-x

DO - 10.1038/s41598-018-36969-x

M3 - Article

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -