Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88

Abstract TLR4 signalling through the MyD88 and TRIF-dependent pathways initiates translocation of the transcription factor NF-κB into the nucleus. In cell population studies using mathematical modeling and functional analyses, Cheng et al. suggested that LPS-driven activation of MyD88, in the absenc...

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Autores principales:	Jiro Sakai, Eugenia Cammarota, John A. Wright, Pietro Cicuta, Rachel A. Gottschalk, Ning Li, Iain D. C. Fraser, Clare E. Bryant
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b745606e97bc4b40a665e75ad37a4268
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spelling	oai:doaj.org-article:b745606e97bc4b40a665e75ad37a42682021-12-02T11:52:21ZLipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD8810.1038/s41598-017-01600-y2045-2322https://doaj.org/article/b745606e97bc4b40a665e75ad37a42682017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01600-yhttps://doaj.org/toc/2045-2322Abstract TLR4 signalling through the MyD88 and TRIF-dependent pathways initiates translocation of the transcription factor NF-κB into the nucleus. In cell population studies using mathematical modeling and functional analyses, Cheng et al. suggested that LPS-driven activation of MyD88, in the absence of TRIF, impairs NF-κB translocation. We tested the model proposed by Cheng et al. using real-time single cell analysis in macrophages expressing EGFP-tagged p65 and a TNFα promoter-driven mCherry. Following LPS stimulation, cells lacking TRIF show a pattern of NF-κB dynamics that is unaltered from wild-type cells, but activation of the TNFα promoter is impaired. In macrophages lacking MyD88, there is minimal NF-κB translocation to the nucleus in response to LPS stimulation, and there is no activation of the TNFα promoter. These findings confirm that signalling through MyD88 is the primary driver for LPS-dependent NF-κB translocation to the nucleus. The pattern of NF-κB dynamics in TRIF-deficient cells does not, however, directly reflect the kinetics of TNFα promoter activation, supporting the concept that TRIF-dependent signalling plays an important role in the transcription of this cytokine.Jiro SakaiEugenia CammarotaJohn A. WrightPietro CicutaRachel A. GottschalkNing LiIain D. C. FraserClare E. BryantNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiro Sakai Eugenia Cammarota John A. Wright Pietro Cicuta Rachel A. Gottschalk Ning Li Iain D. C. Fraser Clare E. Bryant Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88
description	Abstract TLR4 signalling through the MyD88 and TRIF-dependent pathways initiates translocation of the transcription factor NF-κB into the nucleus. In cell population studies using mathematical modeling and functional analyses, Cheng et al. suggested that LPS-driven activation of MyD88, in the absence of TRIF, impairs NF-κB translocation. We tested the model proposed by Cheng et al. using real-time single cell analysis in macrophages expressing EGFP-tagged p65 and a TNFα promoter-driven mCherry. Following LPS stimulation, cells lacking TRIF show a pattern of NF-κB dynamics that is unaltered from wild-type cells, but activation of the TNFα promoter is impaired. In macrophages lacking MyD88, there is minimal NF-κB translocation to the nucleus in response to LPS stimulation, and there is no activation of the TNFα promoter. These findings confirm that signalling through MyD88 is the primary driver for LPS-dependent NF-κB translocation to the nucleus. The pattern of NF-κB dynamics in TRIF-deficient cells does not, however, directly reflect the kinetics of TNFα promoter activation, supporting the concept that TRIF-dependent signalling plays an important role in the transcription of this cytokine.
format	article
author	Jiro Sakai Eugenia Cammarota John A. Wright Pietro Cicuta Rachel A. Gottschalk Ning Li Iain D. C. Fraser Clare E. Bryant
author_facet	Jiro Sakai Eugenia Cammarota John A. Wright Pietro Cicuta Rachel A. Gottschalk Ning Li Iain D. C. Fraser Clare E. Bryant
author_sort	Jiro Sakai
title	Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88
title_short	Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88
title_full	Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88
title_fullStr	Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88
title_full_unstemmed	Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88
title_sort	lipopolysaccharide-induced nf-κb nuclear translocation is primarily dependent on myd88, but tnfα expression requires trif and myd88
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b745606e97bc4b40a665e75ad37a4268
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Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88

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