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Tuberculosis & Respiratory Diseases

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Vol.65 No.4
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Induction Mechanism of PD-L1 (Programmed Cell Death-ligand 1) in Sepsis

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2008, v.65 no.4, pp.343-350

(2008). Induction Mechanism of PD-L1 (Programmed Cell Death-ligand 1) in Sepsis. Tuberculosis & Respiratory Diseases, 65(4), 343-350.
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Abstract

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

keywords
PD-L1, LPS, Sepsis, Macrophage

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