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Overexpression of Gilz Protects Mice Against Lethal Septic Peritonitis

Ballegeer, Marlies*,†; Vandewalle, Jolien*,†; Eggermont, Melanie*,†; Van Isterdael, Gert*,†; Dejager, Lien*,†; De Bus, Liesbet; Decruyenaere, Johan; Vandenbroucke, Roosmarijn E.*,†; Libert, Claude*,†

doi: 10.1097/SHK.0000000000001252
Basic Science Aspects

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 glucocorticoid-induced leucine zipper (GILZ, 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, as the systemic proinflammatory response was not significantly reduced in GILZ-tg mice compared with control mice. During CLP, we observed reduced bacterial counts in blood of GILZ-tg mice compared with 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 with 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.

*VIB Center for Inflammation Research, Ghent, Belgium

Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium

Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium

Address reprint requests to Claude Libert, PhD, VIB Center for Inflammation Research, Technologiepark 927, 9052 Ghent, Belgium. E-mail:

Received 7 June, 2018

Revised 26 June, 2018

Accepted 10 August, 2018

The authors report no conflict of interest.

© 2019 by the Shock Society