Effect and mechanism of saikosaponin A on mouse myeloid-derived suppressor cells

Abstract

Abstract Objective To investigate the effect and mechanism of saikosaponin A (SSA) on mouse myeloid-derived suppressor cells (MDSCs). Methods In vitro: Bone marrow cells (BMC) isolated from normal mouse were treated with Granulocyte-macrophage colony-stimulating factor (GM-CSF) and SSA for 96 h, flow cytometer (FCM) detected the effect of SSA on differentiation of mouse MDSCs. MDSCs were treated with SSA, FCM detected the effect of SSA on apoptosis, LXRα expression, ROS, ARG-1, p-STAT1 and p-NF-κB p65 expression levels. RT-qPCR detected the LXRα and ARG-1 mRNA expression. In vivo: After SSA gavage (ig) and intraperitoneal injection (ip) treatment, FCM detected the proportion of immune cells (T cells, B cells, NK cells, monocytes/macrophages and MDSCs) in the spleen of mice. Results In vitro, SSA could up-regulate the LXRα expression of MDSCs, reduce differentiation of M-MDSCs, induce early apoptosis and decrease the ROS and ARG-1 expression of MDSCs, SSA inhibits STAT1 and NF-κB signaling pathways. In vivo, compared with the control group, SSA up-regulated the proportion of splenic T cells, CD8+T cells and mononuclear/macrophage cells, and decreased the proportion of MDSCs in SSA ip group; SSA up-regulated the proportion of splenic CD8+T cells, B cells and mononuclear/macrophage cells, while decreased the proportion of splenic CD4+T cells and MDSCs in the SSA ig group. Conclusion SSA could regulate differentiation, induce apoptosis of MDSCs, and inhibit their immunosuppressive function, which may be associated with the up-regulation of LXRα expression in MDSCs by SSA. These results may provide a new theoretical basis for the clinical application of SSA.