Article (Scientific journals)
Dual-Specificity Phosphatase Deletion Protects Female, but Not Male, Mice from Endotoxemia- and Polymicrobial-Induced Septic Shock
Vandereyken, Maud; Singh, Pratibha; Wathieu, Caroline et al.
2017In Journal of Immunology
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Abstract :
[en] Dual-specificity phosphatase 3 (DUSP3) is a small phosphatase with poorly known physiological functions and for which only a few substrates are known. Using DUSP3-deficient mice, we recently reported that DUSP3 deficiency confers resistance to endotoxin- and polymicrobial-induced septic shock. We showed that this protection was macrophage dependent. In this study, we further investigated the role of DUSP3 in sepsis tolerance and showed that the resistance is sex dependent. Using adoptive-transfer experiments and ovariectomized mice, we highlighted the role of female sex hormones in the phenotype. Indeed, in ovariectomized female and male mice, the dominance of M2-like macrophages observed in DUSP32/2 female mice was reduced, suggesting a role for this cell subset in sepsis tolerance. At the molecular level, DUSP3 deletion was associated with estrogen dependent decreased phosphorylation of ERK1/2 and Akt in peritoneal macrophages stimulated ex vivo by LPS. Our results demonstrate that estrogens may modulate M2-like responses during endotoxemia in a DUSP3-dependent manner.
Disciplines :
Immunology & infectious disease
Author, co-author :
Vandereyken, Maud
Singh, Pratibha
Wathieu, Caroline ;  Université de Liège > Département de pharmacie > Chimie médicale
Jacques, Sophie ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Zurashvili, Tinatin 
Dejager, Lien
Amand, MAthieu
Musumeci, Lucia ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : GIGA - Cardiovascular Sciences
Singh, Maneesh
MOUTSCHEN, Michel  ;  Centre Hospitalier Universitaire de Liège - CHU > Service des maladies infectieuses - médecine interne
Libert, Claude
Rahmouni, Souad  ;  Université de Liège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Language :
English
Title :
Dual-Specificity Phosphatase Deletion Protects Female, but Not Male, Mice from Endotoxemia- and Polymicrobial-Induced Septic Shock
Publication date :
2017
Journal title :
Journal of Immunology
ISSN :
0022-1767
eISSN :
1550-6606
Publisher :
American Association of Immunologists, Baltimore, United States - Maryland
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 17 September 2017

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