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

Autor: Iris Pinheiro, Lien Dejager, Ioanna Petta, Sofie Vandevyver, Leen Puimège, Tina Mahieu, Marlies Ballegeer, Filip Van Hauwermeiren, Carlo Riccardi, Marnik Vuylsteke, Claude Libert
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 5, Iss 3, Pp 456-470 (2013)
Druh dokumentu: article
ISSN: 20120168
1757-4676
1757-4684
DOI: 10.1002/emmm.201201683
Popis: 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.
Databáze: Directory of Open Access Journals
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