Dexamethasone Reduces Viability of Bone Marrow Derived Macrophages

Abstract

Abstract 4732Glucocorticoids are steroid hormones with pleotropic effects and are widely used in clinical practice. Glucocorticoids affect almost every cell of the immune system. Here, we show that dexamethasone (DEX), a synthetic glucocorticoid, decreases viability of naïve bone marrow-derived macrophages (BMDM) in a dose dependent manner. A 24-hour incubation with 0.1, 0.5 and 1 microM DEX reduced BMDM viability by 22%, 26% and 34%, respectively, compared with untreated cells. Annexin-PI staining suggests an apoptotic mechanism. Administration of DEX in the presence of lipopolysaccharide (LPS) protected the BMDM against DEX-mediated cell death.In addition to its effect on cell viability, DEX also significantly reduced the percentage of BMDM expressing high levels of the differentiation and activation markers F4/80 and CD11b (5 fold decrease mediated by 1 microM DEX). Treatment of BMDM with 1 microM DEX also led to a ∼ 50% decrease in macrophage inflammatory protein 1 alpha (MIP-1-alpha) mRNA expression levels.These findings may contribute to a better understanding of DEX effects on naïve and activated macrophages and may have clinical implications in various diseases, including infection, inflammation and neoplastic diseases.Glucocorticoids are steroid hormones with pleotropic effects and are widely used in clinical practice. Glucocorticoids affect almost every cell of the immune system. Here, we show that dexamethasone (DEX), a synthetic glucocorticoid, decreases viability of naïve bone marrow-derived macrophages (BMDM) in a dose dependent manner. A 24-hour incubation with 0.1, 0.5 and 1 microM DEX reduced BMDM viability by 22%, 26% and 34%, respectively, compared with untreated cells. Annexin-PI staining suggests an apoptotic mechanism. Administration of DEX in the presence of lipopolysaccharide (LPS) protected the BMDM against DEX-mediated cell death.In addition to its effect on cell viability, DEX also significantly reduced the percentage of BMDM expressing high levels of the differentiation and activation markers F4/80 and CD11b (5 fold decrease mediated by 1 microM DEX). Treatment of BMDM with 1 microM DEX also led to a ∼ 50% decrease in macrophage inflammatory protein 1 alpha (MIP-1-alpha) mRNA expression levels.These findings may contribute to a better understanding of DEX effects on naïve and activated macrophages and may have clinical implications in various diseases, including infection, inflammation and neoplastic diseases.v Disclosures:No relevant conflicts of interest to declare.