Immunomodulatory effects of glucocorticoid-induced leucine zipper (GILZ) expression in murine bone-marrow derived macrophages.
Here, we provide evidence for the immunomodulatory effects of glucocorticoid-induced leucine zipper (GILZ) overexpression in macrophages, demonstrating enhanced antibacterial activity, protection from pyroptosis, and altered mitochondrial function. Additionally, our findings reveal a significant impact on MMP activity, suggesting a role for GILZ in influencing extracellular matrix remodeling and wound healing processes. The study contributes to explorations of GILZ in its significance in pro-resolving macrophage functions. Overall design: B6.129P2-Lyz2tm1(cre)Ifo/J mice with Cre recombinase expression under the endogenous Lyz2 promotor of the myeloid cell lineage were crossed with mice bearing loxP sites up and downstream of Gilz exon 6 resulting in a myeloid-specific knockout of GILZ (B6.129P2 Tsc22d3f/f Lyz2tm1(cre)Ifo/J, GILZ KO) (Bruscoli et al., 2012). In addition, mice bearing a Tsc22d3/Gilz-1 cDNA knock-in under the control of the ROSA26 promoter preceded by a loxP-flanked stop cassette (Carceller et al., 2016) were crossed with B6.129P2-Lyz2tm1(cre)Ifo/J mice, resulting in myeloid-specific GILZ overexpression. Employing RNA sequencing, we examined wild-type (WT), GILZ knockout (GILZ KO), and GILZ overexpressing (GILZ TG) bone-marrow derived macrophages (BMM) under untreated conditions and following 4 h lipopolysaccharide (LPS) treatment. All analyses were conducted in the R programming language. DESeq2 analysis revealed differentially expressed genes (DEGs, p < 0.05) in the comparisons of GILZ KO vs. WT, GILZ TG vs. WT, and GILZ KO vs. GILZ TG under both untreated and LPS-treated conditions.