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

Iris Pinheiro UGent, Lien Dejager, Ioanna Petta UGent, Sofie Vandevyver, Leen Puimège, Tina Mahieu, Marlies Ballegeer UGent, Filip Van Hauwermeiren, Carlo Riccardi, Marnik Vuylsteke UGent, et al. (2013) EMBO MOLECULAR MEDICINE. 5(3). p.456-470
abstract
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
INDUCED LEUCINE-ZIPPER, SPLENIC IMMUNE FUNCTIONS, X chromosome, SPRET/Ei, LPS, inflammation, Gilz, FEMALES, PROTEIN, SEPSIS, EXPRESSION, MOUSE STRAIN SPRET/EI, FACTOR-KAPPA-B, GLUCOCORTICOID-RECEPTOR, ALVEOLAR MACROPHAGES
journal title
EMBO MOLECULAR MEDICINE
EMBO Mol. Med.
volume
5
issue
3
pages
456 - 470
Web of Science type
Article
Web of Science id
000315861200012
JCR category
MEDICINE, RESEARCH & EXPERIMENTAL
JCR impact factor
8.245 (2013)
JCR rank
8/124 (2013)
JCR quartile
1 (2013)
ISSN
1757-4676
DOI
10.1002/emmm.201201683
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
3182293
handle
http://hdl.handle.net/1854/LU-3182293
date created
2013-04-04 09:24:18
date last changed
2018-07-01 10:11:08
@article{3182293,
  abstract     = {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.},
  author       = {Pinheiro, Iris and Dejager, Lien and Petta, Ioanna and Vandevyver, Sofie and Puim{\`e}ge, Leen and Mahieu, Tina and Ballegeer, Marlies and Van Hauwermeiren, Filip and Riccardi, Carlo and Vuylsteke, Marnik and Libert, Claude},
  issn         = {1757-4676},
  journal      = {EMBO MOLECULAR MEDICINE},
  keyword      = {INDUCED LEUCINE-ZIPPER,SPLENIC IMMUNE FUNCTIONS,X chromosome,SPRET/Ei,LPS,inflammation,Gilz,FEMALES,PROTEIN,SEPSIS,EXPRESSION,MOUSE STRAIN SPRET/EI,FACTOR-KAPPA-B,GLUCOCORTICOID-RECEPTOR,ALVEOLAR MACROPHAGES},
  language     = {eng},
  number       = {3},
  pages        = {456--470},
  title        = {LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome},
  url          = {http://dx.doi.org/10.1002/emmm.201201683},
  volume       = {5},
  year         = {2013},
}

Chicago
Pinheiro, Iris, Lien Dejager, Ioanna Petta, Sofie Vandevyver, Leen Puimège, Tina Mahieu, Marlies Ballegeer, et al. 2013. “LPS Resistance of SPRET/Ei Mice Is Mediated by Gilz, Encoded by the Tsc22d3 Gene on the X Chromosome.” Embo Molecular Medicine 5 (3): 456–470.
APA
Pinheiro, I., Dejager, L., Petta, I., Vandevyver, S., Puimège, L., Mahieu, T., Ballegeer, M., et al. (2013). LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome. EMBO MOLECULAR MEDICINE, 5(3), 456–470.
Vancouver
1.
Pinheiro I, Dejager L, Petta I, Vandevyver S, Puimège L, Mahieu T, et al. LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome. EMBO MOLECULAR MEDICINE. 2013;5(3):456–70.
MLA
Pinheiro, Iris, Lien Dejager, Ioanna Petta, et al. “LPS Resistance of SPRET/Ei Mice Is Mediated by Gilz, Encoded by the Tsc22d3 Gene on the X Chromosome.” EMBO MOLECULAR MEDICINE 5.3 (2013): 456–470. Print.