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Dual-specificity phosphatase 3 deletion protects female, but not male, mice from endotoxemia-induced and polymicrobial-induced septic shock

(2017) JOURNAL OF IMMUNOLOGY. 199(7). p.2515-2527
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Abstract
Dual-specificity phosphatase 3 (DUSP3) is a small phosphatase with poorly known physiological functions and for which only a few substrates are known. Using knockout 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 females and in male mice, the dominance of M2-like macrophages observed in DUSP3(-/-) 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.
Keywords
ESTROGEN-RECEPTOR, MACROPHAGE SUBSETS, GENE-EXPRESSION, VHR PHOSPHATASE, SEX-HORMONES, C-JUN, SEPSIS, ACTIVATION, DISEASE, GENDER

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Chicago
Vandereyken, Maud M, Pratibha Singh, Caroline P Wathieu, Sophie Jacques, Tinatin Zurashvilli, Lien Dejager, Mathieu Amand, et al. 2017. “Dual-specificity Phosphatase 3 Deletion Protects Female, but Not Male, Mice from Endotoxemia-induced and Polymicrobial-induced Septic Shock.” Journal of Immunology 199 (7): 2515–2527.
APA
Vandereyken, M. M., Singh, P., Wathieu, C. P., Jacques, S., Zurashvilli, T., Dejager, L., Amand, M., et al. (2017). Dual-specificity phosphatase 3 deletion protects female, but not male, mice from endotoxemia-induced and polymicrobial-induced septic shock. JOURNAL OF IMMUNOLOGY, 199(7), 2515–2527.
Vancouver
1.
Vandereyken MM, Singh P, Wathieu CP, Jacques S, Zurashvilli T, Dejager L, et al. Dual-specificity phosphatase 3 deletion protects female, but not male, mice from endotoxemia-induced and polymicrobial-induced septic shock. JOURNAL OF IMMUNOLOGY. 2017;199(7):2515–27.
MLA
Vandereyken, Maud M, Pratibha Singh, Caroline P Wathieu, et al. “Dual-specificity Phosphatase 3 Deletion Protects Female, but Not Male, Mice from Endotoxemia-induced and Polymicrobial-induced Septic Shock.” JOURNAL OF IMMUNOLOGY 199.7 (2017): 2515–2527. Print.
@article{8533762,
  abstract     = {Dual-specificity phosphatase 3 (DUSP3) is a small phosphatase with poorly known physiological functions and for which only a few substrates are known. Using knockout 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 females and in male mice, the dominance of M2-like macrophages observed in DUSP3(-/-) 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.},
  author       = {Vandereyken, Maud M and Singh, Pratibha and Wathieu, Caroline P and Jacques, Sophie and Zurashvilli, Tinatin and Dejager, Lien and Amand, Mathieu and Musumeci, Lucia and Singh, Maneesh and Moutschen, Michel P and Libert, Claude and Rahmouni, Souad},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  language     = {eng},
  number       = {7},
  pages        = {2515--2527},
  title        = {Dual-specificity phosphatase 3 deletion protects female, but not male, mice from endotoxemia-induced and polymicrobial-induced septic shock},
  url          = {http://dx.doi.org/10.4049/jimmunol.1602092},
  volume       = {199},
  year         = {2017},
}

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