Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis

Abstract Map3k8 has been proposed as a useful target for the treatment of inflammatory diseases. We show here that during lipopolysaccharide-induced emergency granulopoiesis, Map3k8 deficiency strongly impairs the increase in circulating mature (Ly6GhighCD11b+) and immature (Ly6GlowCD11b+) neutrophi...

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Autores principales:	Ángela Sánchez, Carlos Relaño, Araceli Carrasco, Constanza Contreras-Jurado, Antonio Martín-Duce, Ana Aranda, Susana Alemany
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/93e9a5c5bb6f40639afeb9e2aed48bd6
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spelling	oai:doaj.org-article:93e9a5c5bb6f40639afeb9e2aed48bd62021-12-02T16:06:03ZMap3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis10.1038/s41598-017-04538-32045-2322https://doaj.org/article/93e9a5c5bb6f40639afeb9e2aed48bd62017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04538-3https://doaj.org/toc/2045-2322Abstract Map3k8 has been proposed as a useful target for the treatment of inflammatory diseases. We show here that during lipopolysaccharide-induced emergency granulopoiesis, Map3k8 deficiency strongly impairs the increase in circulating mature (Ly6GhighCD11b+) and immature (Ly6GlowCD11b+) neutrophils. After chimaeric bone marrow (BM) transplantation into recipient Map3k8−/− mice, lipopolysaccharide treatment did not increase circulating Ly6GhighCD11b+ cells and strongly decreased circulating Ly6GlowCD11b+ cells. Lipopolysaccharide-treated Map3k8−/− mice showed decreased production of granulocyte colony-stimulating factor (G-CSF), a key factor in neutrophil expansion, and a Map3k8 inhibitor blocked lipopolysaccharide-mediated G-CSF expression in endothelial cell lines. Ly6GlowCD11b+ BM cells from lipopolysaccharide-treated Map3k8−/− mice displayed impaired expression of CCAAT-enhancer-binding protein β, which depends on G-CSF for expression and is crucial for cell cycle acceleration in this life-threatening condition. Accordingly, lipopolysaccharide-treated Map3k8−/− mice showed decreased Ly6GlowCD11b+ BM cell proliferation, as evidenced by a decrease in the percentage of the most immature precursors, which have the highest proliferation capacity among this cell population. Thus, Map3k8 expression by non-haematopoietic tissue is required for lipopolysaccharide-induced emergency granulopoiesis. The novel observation that inhibition of Map3k8 activity decreases neutrophilia during life-threatening systemic infection suggests a possible risk in the proposed use of Map3k8 blockade as an anti-inflammatory therapy.Ángela SánchezCarlos RelañoAraceli CarrascoConstanza Contreras-JuradoAntonio Martín-DuceAna ArandaSusana AlemanyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ángela Sánchez Carlos Relaño Araceli Carrasco Constanza Contreras-Jurado Antonio Martín-Duce Ana Aranda Susana Alemany Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis
description	Abstract Map3k8 has been proposed as a useful target for the treatment of inflammatory diseases. We show here that during lipopolysaccharide-induced emergency granulopoiesis, Map3k8 deficiency strongly impairs the increase in circulating mature (Ly6GhighCD11b+) and immature (Ly6GlowCD11b+) neutrophils. After chimaeric bone marrow (BM) transplantation into recipient Map3k8−/− mice, lipopolysaccharide treatment did not increase circulating Ly6GhighCD11b+ cells and strongly decreased circulating Ly6GlowCD11b+ cells. Lipopolysaccharide-treated Map3k8−/− mice showed decreased production of granulocyte colony-stimulating factor (G-CSF), a key factor in neutrophil expansion, and a Map3k8 inhibitor blocked lipopolysaccharide-mediated G-CSF expression in endothelial cell lines. Ly6GlowCD11b+ BM cells from lipopolysaccharide-treated Map3k8−/− mice displayed impaired expression of CCAAT-enhancer-binding protein β, which depends on G-CSF for expression and is crucial for cell cycle acceleration in this life-threatening condition. Accordingly, lipopolysaccharide-treated Map3k8−/− mice showed decreased Ly6GlowCD11b+ BM cell proliferation, as evidenced by a decrease in the percentage of the most immature precursors, which have the highest proliferation capacity among this cell population. Thus, Map3k8 expression by non-haematopoietic tissue is required for lipopolysaccharide-induced emergency granulopoiesis. The novel observation that inhibition of Map3k8 activity decreases neutrophilia during life-threatening systemic infection suggests a possible risk in the proposed use of Map3k8 blockade as an anti-inflammatory therapy.
format	article
author	Ángela Sánchez Carlos Relaño Araceli Carrasco Constanza Contreras-Jurado Antonio Martín-Duce Ana Aranda Susana Alemany
author_facet	Ángela Sánchez Carlos Relaño Araceli Carrasco Constanza Contreras-Jurado Antonio Martín-Duce Ana Aranda Susana Alemany
author_sort	Ángela Sánchez
title	Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis
title_short	Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis
title_full	Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis
title_fullStr	Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis
title_full_unstemmed	Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis
title_sort	map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/93e9a5c5bb6f40639afeb9e2aed48bd6
work_keys_str_mv	AT angelasanchez map3k8controlsgranulocytecolonystimulatingfactorproductionandneutrophilprecursorproliferationinlipopolysaccharideinducedemergencygranulopoiesis AT carlosrelano map3k8controlsgranulocytecolonystimulatingfactorproductionandneutrophilprecursorproliferationinlipopolysaccharideinducedemergencygranulopoiesis AT aracelicarrasco map3k8controlsgranulocytecolonystimulatingfactorproductionandneutrophilprecursorproliferationinlipopolysaccharideinducedemergencygranulopoiesis AT constanzacontrerasjurado map3k8controlsgranulocytecolonystimulatingfactorproductionandneutrophilprecursorproliferationinlipopolysaccharideinducedemergencygranulopoiesis AT antoniomartinduce map3k8controlsgranulocytecolonystimulatingfactorproductionandneutrophilprecursorproliferationinlipopolysaccharideinducedemergencygranulopoiesis AT anaaranda map3k8controlsgranulocytecolonystimulatingfactorproductionandneutrophilprecursorproliferationinlipopolysaccharideinducedemergencygranulopoiesis AT susanaalemany map3k8controlsgranulocytecolonystimulatingfactorproductionandneutrophilprecursorproliferationinlipopolysaccharideinducedemergencygranulopoiesis
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Map3k8 controls granulocyte colony-stimulating factor production and neutrophil precursor proliferation in lipopolysaccharide-induced emergency granulopoiesis

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