Sirtuin 6 mitigated LPS‐induced human umbilical vein endothelial cells inflammatory responses through modulating nuclear factor erythroid 2‐related factor 2

Background Nuclear factor erythroid 2‐related factor 2 (Nrf2) protects the lung from sepsis‐induced injury through activating Nrf2‐regulated multiple phase 2 detoxification genes, including NAD(P)H: quinine oxidoreductase‐1 (NQO1) and heme oxygenase‐1 (HO1). Based on the positive effect of Sirtuin 6 on Nrf2, we aim to explore the potential role of SIRT6 in the mechanism of sepsis‐induced acute lung injury (ALI). Methods Mouse models of sepsis were constructed by instilling intratracheal of lipopolysaccharide (LPS; 4 ml/kg). After 48‐hour treatment, lung tissues were collected to measure the degree of lung injury. The SIRT6, siSIRT6, and siNrf2 plasmids were cotransfected into various concentrations of LPS‐treated human umbilical vein endothelial cells (HUVECs; 0, 1, 5, 10, and 50 μg/ml) using Lipofectamine 2000. Tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐6 levels were determined by enzyme‐linked immunosorbent assay. Expression levels of SIRT6, Nrf2, NQO1, and HO1 was measured by quantitative polymerase chain reaction and Western blot analysis. Cell apoptosis was determined by flow cytometry. Results Lung tissues in the model group already had basic characteristics of ALI. Compared with the control model, TNF‐α and IL‐6 levels were much higher (P