Glucocorticoid-Induced Leucine Zipper Is Expressed in Human Neutrophils and Promotes Apoptosis through Mcl-1 Down-Regulation

Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein, the expression of which is mainly induced by glucocorticoids (GCs) in haematopoietic cells. GILZ regulates signal transduction pathways of inflammation and plays a role in cell survival. The objective of this study was to evaluate the expression and mechanisms of action of GILZ in the apoptosis of human neutrophils. GILZ expression was induced by GCs in human neutrophils, enhanced upon phosphatidylinositol 3-kinase inhibition and resulted in apoptosis amplification. We then stably transfected PLB-985 cells with the human gilz gene and differentiated both control and GILZ-overexpressing clones in neutrophillike cells. GILZ overexpression in PLB-985 cells led to an exacerbated apoptosis, associated with caspase-3, caspase-9 and caspase-8 activations, and a loss of mitochondrial potential, suggesting that GILZ-induced apoptosis used the mitochondrial pathway. The expression of BH3 interacting domain death agonist, Bcl-2 interacting mediator of cell death, annexin-A1 and Bcl-2-associated X was not affected in PLBReceived: May 7, 2015 Accepted after revision: July 29, 2015 Published online: September 19, 2015 Journal of Innate Immunity Dr. Armelle Biola-Vidamment INSERM UMR-996, Faculté de Pharmacie, Université Paris-Sud 5, Rue JB Clément FR–92296 Châtenay-Malabry Cedex (France) E-Mail armelle.biola-vidamment @ u-psud.fr © 2015 S. Karger AG, Basel 1662–811X/15/0081–0081$39.50/0