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LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome

Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to d...

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Autores principales: Pinheiro, Iris, Dejager, Lien, Petta, Ioanna, Vandevyver, Sofie, Puimège, Leen, Mahieu, Tina, Ballegeer, Marlies, Van Hauwermeiren, Filip, Riccardi, Carlo, Vuylsteke, Marnik, Libert, Claude
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598084/
https://www.ncbi.nlm.nih.gov/pubmed/23495141
http://dx.doi.org/10.1002/emmm.201201683
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author Pinheiro, Iris
Dejager, Lien
Petta, Ioanna
Vandevyver, Sofie
Puimège, Leen
Mahieu, Tina
Ballegeer, Marlies
Van Hauwermeiren, Filip
Riccardi, Carlo
Vuylsteke, Marnik
Libert, Claude
author_facet Pinheiro, Iris
Dejager, Lien
Petta, Ioanna
Vandevyver, Sofie
Puimège, Leen
Mahieu, Tina
Ballegeer, Marlies
Van Hauwermeiren, Filip
Riccardi, Carlo
Vuylsteke, Marnik
Libert, Claude
author_sort Pinheiro, Iris
collection PubMed
description Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis.
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spelling pubmed-35980842013-03-19 LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome Pinheiro, Iris Dejager, Lien Petta, Ioanna Vandevyver, Sofie Puimège, Leen Mahieu, Tina Ballegeer, Marlies Van Hauwermeiren, Filip Riccardi, Carlo Vuylsteke, Marnik Libert, Claude EMBO Mol Med Research Articles Natural variation for LPS-induced lethal inflammation in mice is useful for identifying new genes that regulate sepsis, which could form the basis for novel therapies for systemic inflammation in humans. Here we report that LPS resistance of the inbred mouse strain SPRET/Ei, previously reported to depend on the glucocorticoid receptor (GR), maps to the distal region of the X-chromosome. The GR-inducible gene Tsc22d3, encoding the protein Gilz and located in the critical region on the X-chromosome, showed a higher expressed SPRET/Ei allele, regulated in cis. Higher Gilz levels were causally related to reduced inflammation, as shown with knockdown and overexpression studies in macrophages. Transient overexpression of Gilz by hydrodynamic plasmid injection confirmed that Gilz protects mice against endotoxemia Our data strongly suggest that Gilz is responsible for the LPS resistance of SPRET/Ei mice and that it could become a treatment option for sepsis. WILEY-VCH Verlag 2013-03 2013-03-05 /pmc/articles/PMC3598084/ /pubmed/23495141 http://dx.doi.org/10.1002/emmm.201201683 Text en Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Research Articles
Pinheiro, Iris
Dejager, Lien
Petta, Ioanna
Vandevyver, Sofie
Puimège, Leen
Mahieu, Tina
Ballegeer, Marlies
Van Hauwermeiren, Filip
Riccardi, Carlo
Vuylsteke, Marnik
Libert, Claude
LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome
title LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome
title_full LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome
title_fullStr LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome
title_full_unstemmed LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome
title_short LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome
title_sort lps resistance of spret/ei mice is mediated by gilz, encoded by the tsc22d3 gene on the x chromosome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598084/
https://www.ncbi.nlm.nih.gov/pubmed/23495141
http://dx.doi.org/10.1002/emmm.201201683
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