Overexpressed CD39 mitigates sepsis‑induced kidney epithelial cell injury via suppressing the activation of NLR family pyrin domain containing 3.

Abstract

Unfettered inflammation is a leading cause of multiple organ failures in sepsis. The anti-inflammatory role of cluster of differentiation (CD)39 has been previously reported. The present study aimed to investigate the role of unfettered inflammation in sepsis-induced acute kidney injury (AKI). Lipopolysaccharide (LPS) was introduced to construct a sepsis mouse model. Kidney function and pathological changes in mice were measured at 12, 24 and 48 h. CD39 overexpression and inhibition vectors were transfected into renal tubular epithelial (HK-2) cells, followed by LPS treatment (10 μg/ml), and the cell viability changes at 24 h after treatment were assessed and the expression of NLR family pyrin domain containing 3 (NLRP3), cleaved caspase-1 and CD39 were determined by performing ELISAs. Cell apoptosis and reactive oxygen species (ROS) levels were determined by flow cytometry. It was found that after LPS administration, kidney injury was the most serious at 24 h in mice. CD39 overexpression could suppress the upregulation of pro-inflammatory cytokines induced by LPS treatment. In addition, the cell apoptosis and ROS level exhibited an obvious decrease, while cell viability increased. The NLRP3 expression and activity also showed a great inhibition in CD39-overexpressed cells. By contrast to CD39 overexpression, CD39 inhibition promoted the activation of the NLRP3 inflammasome. These data indicate the protective role of CD39 in LPS-induced renal tubular epithelial cell damage through inhibiting NLRP3 inflammasome activation and that CD39 might be a potential therapeutic target in sepsis-induced AKI.