Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency

Abstract Stimulation with lipopolysaccharide (LPS; endotoxin) not only causes rapid production of proinflammatory cytokines, but also induces a state of LPS hypo-responsiveness to a second LPS stimulation (endotoxin tolerance (ET)). Murine bone marrow-derived MCs (BMMCs) and peritoneal MCs (PMCs) de...

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Autores principales:	Magdalena Poplutz, Maryna Levikova, Juliane Lüscher-Firzlaff, Marina Lesina, Hana Algül, Bernhard Lüscher, Michael Huber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54e08d040c3b40868838fe4f8e75069e
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spelling	oai:doaj.org-article:54e08d040c3b40868838fe4f8e75069e2021-12-02T11:53:00ZEndotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency10.1038/s41598-017-04890-42045-2322https://doaj.org/article/54e08d040c3b40868838fe4f8e75069e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04890-4https://doaj.org/toc/2045-2322Abstract Stimulation with lipopolysaccharide (LPS; endotoxin) not only causes rapid production of proinflammatory cytokines, but also induces a state of LPS hypo-responsiveness to a second LPS stimulation (endotoxin tolerance (ET)). Murine bone marrow-derived MCs (BMMCs) and peritoneal MCs (PMCs) developed ET as shown by an abrogated production of Il6/Tnf RNAs and IL-6/TNF-α proteins. In naive BMMCs, LPS stimulation induced a transient decline in the trimethylation of lysine 9 of the core histone H3 (H3K9me3), a suppressive chromatin mark, at the Il6/Tnf promoters, which correlated with p50(NFκB) and p65(NFκB) binding. Both demethylation and NFκB binding were abrogated in tolerant cells. In addition, cytosolic NFκB activation was suppressed in tolerant BMMCs. Intriguingly, antigen stimulation of naive and tolerant MCs induced comparable production of Il6/Tnf and IL-6/TNF-α, although ET also affected antigen-triggered activation of NFκB; pharmacological analysis indicated the importance of Ca2+-dependent transcription in this respect. In macrophages, the IκB member BCL3 is induced by LPS and known to be involved in ET, which was not corroborated comparing wild-type and Bcl3-deficient BMMCs. Interestingly, Bcl3-deficient PMCs produce markedly increased amounts of IL-6/TNF-α after LPS stimulation. Collectively, ET in MCs is BCL3-independent, however, in PMCs, BCL3 negatively regulates immediate LPS-induced cytokine production and quantitatively affects ET.Magdalena PoplutzMaryna LevikovaJuliane Lüscher-FirzlaffMarina LesinaHana AlgülBernhard LüscherMichael HuberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Magdalena Poplutz Maryna Levikova Juliane Lüscher-Firzlaff Marina Lesina Hana Algül Bernhard Lüscher Michael Huber Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency
description	Abstract Stimulation with lipopolysaccharide (LPS; endotoxin) not only causes rapid production of proinflammatory cytokines, but also induces a state of LPS hypo-responsiveness to a second LPS stimulation (endotoxin tolerance (ET)). Murine bone marrow-derived MCs (BMMCs) and peritoneal MCs (PMCs) developed ET as shown by an abrogated production of Il6/Tnf RNAs and IL-6/TNF-α proteins. In naive BMMCs, LPS stimulation induced a transient decline in the trimethylation of lysine 9 of the core histone H3 (H3K9me3), a suppressive chromatin mark, at the Il6/Tnf promoters, which correlated with p50(NFκB) and p65(NFκB) binding. Both demethylation and NFκB binding were abrogated in tolerant cells. In addition, cytosolic NFκB activation was suppressed in tolerant BMMCs. Intriguingly, antigen stimulation of naive and tolerant MCs induced comparable production of Il6/Tnf and IL-6/TNF-α, although ET also affected antigen-triggered activation of NFκB; pharmacological analysis indicated the importance of Ca2+-dependent transcription in this respect. In macrophages, the IκB member BCL3 is induced by LPS and known to be involved in ET, which was not corroborated comparing wild-type and Bcl3-deficient BMMCs. Interestingly, Bcl3-deficient PMCs produce markedly increased amounts of IL-6/TNF-α after LPS stimulation. Collectively, ET in MCs is BCL3-independent, however, in PMCs, BCL3 negatively regulates immediate LPS-induced cytokine production and quantitatively affects ET.
format	article
author	Magdalena Poplutz Maryna Levikova Juliane Lüscher-Firzlaff Marina Lesina Hana Algül Bernhard Lüscher Michael Huber
author_facet	Magdalena Poplutz Maryna Levikova Juliane Lüscher-Firzlaff Marina Lesina Hana Algül Bernhard Lüscher Michael Huber
author_sort	Magdalena Poplutz
title	Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency
title_short	Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency
title_full	Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency
title_fullStr	Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency
title_full_unstemmed	Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency
title_sort	endotoxin tolerance in mast cells, its consequences for ige-mediated signalling, and the effects of bcl3 deficiency
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/54e08d040c3b40868838fe4f8e75069e
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Endotoxin tolerance in mast cells, its consequences for IgE-mediated signalling, and the effects of BCL3 deficiency

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