Monitoring Atsttrin-Mediated Inhibition of TNFα/NF-κß Activation Through In Vivo Bioluminescence Imaging.
Methods Mol Biol
; 2248: 201-210, 2021.
Article
em En
| MEDLINE
| ID: mdl-33185877
ABSTRACT
The NF-κß transcription factor is a molecular mediator crucial to many biological functions and a central regulator of inflammatory and immune responses. NF-κß is activated by multiple immunologically relevant stimuli, including members of the tumor necrosis factor (TNF) superfamily, and targeting TNF/NFκß activity is a therapeutic objective in many inflammatory and autoimmune conditions. Here, we describe the generation of a transgenic reporter mouse model, expressing the human tumor necrosis factor α (TNF-α) transgene (TNF-tg) and carrying the luciferase gene under control of the NFκB-responsive element (NF-κB-Luc). Bioluminescence imaging shows that overexpression of TNF-α effectively activates NF-κB luciferase in vivo. To evaluate this system as a screen for potential therapeutics targeting the TNF/NFκß signaling pathway, we treated double mutant mice with PGRN-derived Atsttrin, an engineered molecule comprising the minimal progranulin (PGRN)TNFR binding fragments previously demonstrated as therapeutic in multiple models of TNF/NFκß-driven disease. Administration of Atsttrin could effectively inhibit luciferase activity in TNF-tgNF-κB-Luc double mutant mice and demonstrates that this transgenic model can be used to non-invasively monitor the in vivo efficacy of modulators of TNF-activated NF-κB signaling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
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Fator de Necrose Tumoral alfa
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Imagem Molecular
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Progranulinas
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Medições Luminescentes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article