Induction Mechanism of PD-L1 (Programmed Cell Death-ligand 1) in Sepsis

PD-L1 is expressed in a variety of antigen-presenting cells and provides T cell tolerance via ligation with its receptor PD-1 and B7-1 on T cells.Stimulation with lipopolysaccharide (LPS) can increase the level of PD-L1 expression in B cells and macrophages, which suggests that this molecule plays a role in the immunosuppression observed in severe sepsis.The aim of this study was to identify which of the downstream pathways of TLR4 are involved in the up-regulation of PD-L1 by LPS in macrophages.Flow cytometry was used to examine the expression of PD-L1 in RAW 264.7 macrophages stimulated with LPS.The following chemical inhibitors were used to evaluate the role of each pathway: LY294002 for PI3K/Akt, SB202190 for p38 MAPK, and U0126 for MEK.LPS induced the expression of PD-L1 in a time-and dose-dependent manner.Transfection of siRNA for TLR4 suppressed the induction of PD-L1.Pretreatment with LY294002 and SB202190 decreased the level of PD-L1 expression but U0126 did not.Overall, the PI3K/Akt and p38 MAPK pathways are involved in the up-regulation of PD-L1 expression in RAW 264.7 macrophages stimulated with LPS. (