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Overexpression of Gilz protects mice against lethal septic peritonitis

Marlies Ballegeer (UGent) , Jolien Vandewalle (UGent) , Melanie Eggermont (UGent) , Gert Van Isterdael (UGent) , Lien Dejager (UGent) , Liesbet De Bus (UGent) , Johan Decruyenaere (UGent) , Roosmarijn Vandenbroucke (UGent) and Claude Libert (UGent)
(2019) SHOCK.
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Abstract
Sepsis in humans and experimental animals is characterized by an acute inflammatory response. Glucocorticoids (GCs) are widely used for the treatment of many inflammatory disorders, yet their effectiveness in sepsis is debatable. One of the major anti-inflammatory proteins induced by GCs is GILZ (Glucocorticoid-Induced Leucine Zipper, coded by the TSC22D3 gene). We found that TSC22D3 mRNA expression is downregulated in white blood cells of human sepsis patients. Interestingly, transgenic Gilz overexpressing mice (Gilz-tg) showed better survival rates in the cecal ligation and puncture (CLP) model of mouse sepsis. To our surprise, Gilz had only mild anti-inflammatory effects in this model, since the systemic pro-inflammatory response was not significantly reduced in Gilz-tg mice compared to control mice. During CLP, we observed reduced bacterial counts in blood of Gilz-tg mice compared to control mice. We found increased expression of Tsc22d3 mRNA specifically in peritoneal exudate cells in the CLP model, as well as increased capacity for bacterial phagocytosis of CD45 Gilz-tg cells compared to CD45 Gilz-wt cells. Hence, we believe that the protective effects of GILZ in the CLP model can be linked to a more efficient phagocytosis.
Keywords
Critical Care and Intensive Care Medicine, Emergency Medicine

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Chicago
Ballegeer, Marlies, Jolien Vandewalle, Melanie Eggermont, Gert Van Isterdael, Lien Dejager, Liesbet De Bus, Johan Decruyenaere, Roosmarijn Vandenbroucke, and Claude Libert. 2019. “Overexpression of Gilz Protects Mice Against Lethal Septic Peritonitis.” Shock.
APA
Ballegeer, M., Vandewalle, J., Eggermont, M., Van Isterdael, G., Dejager, L., De Bus, L., Decruyenaere, J., et al. (2019). Overexpression of Gilz protects mice against lethal septic peritonitis. SHOCK.
Vancouver
1.
Ballegeer M, Vandewalle J, Eggermont M, Van Isterdael G, Dejager L, De Bus L, et al. Overexpression of Gilz protects mice against lethal septic peritonitis. SHOCK. 2019;
MLA
Ballegeer, Marlies et al. “Overexpression of Gilz Protects Mice Against Lethal Septic Peritonitis.” SHOCK (2019): n. pag. Print.
@article{8582564,
  abstract     = {Sepsis in humans and experimental animals is characterized by an acute inflammatory response. Glucocorticoids (GCs) are widely used for the treatment of many inflammatory disorders, yet their effectiveness in sepsis is debatable. One of the major anti-inflammatory proteins induced by GCs is GILZ (Glucocorticoid-Induced Leucine Zipper, coded by the TSC22D3 gene). We found that TSC22D3 mRNA expression is downregulated in white blood cells of human sepsis patients. Interestingly, transgenic Gilz overexpressing mice (Gilz-tg) showed better survival rates in the cecal ligation and puncture (CLP) model of mouse sepsis. To our surprise, Gilz had only mild anti-inflammatory effects in this model, since the systemic pro-inflammatory response was not significantly reduced in Gilz-tg mice compared to control mice. During CLP, we observed reduced bacterial counts in blood of Gilz-tg mice compared to control mice. We found increased expression of Tsc22d3 mRNA specifically in peritoneal exudate cells in the CLP model, as well as increased capacity for bacterial phagocytosis of CD45 Gilz-tg cells compared to CD45 Gilz-wt cells. Hence, we believe that the protective effects of GILZ in the CLP model can be linked to a more efficient phagocytosis.},
  author       = {Ballegeer, Marlies and Vandewalle, Jolien and Eggermont, Melanie and Van Isterdael, Gert and Dejager, Lien and De Bus, Liesbet and Decruyenaere, Johan and Vandenbroucke, Roosmarijn and Libert, Claude},
  issn         = {1073-2322},
  journal      = {SHOCK},
  language     = {eng},
  title        = {Overexpression of Gilz protects mice against lethal septic peritonitis},
  url          = {http://dx.doi.org/10.1097/shk.0000000000001252},
  year         = {2019},
}

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