Department of Gastroenterology, Shanghai Tongren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.
Department of Gastroenterology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
Mol Med Rep. 2018 May;17(5):6847-6851. doi: 10.3892/mmr.2018.8641. Epub 2018 Feb 27.
Ebselen is a seleno-organic compound that has been demonstrated to have antioxidant and anti-inflammatory properties. A previous study determined that ebselen inhibits airway inflammation induced by inhalational lipopolysaccharide (LPS), however, the underlying molecular mechanism remains to be elucidated. The present study investigated the effect of ebselen on the glutathione peroxidase (GPX)‑reactive oxygen species (ROS) pathway and interleukin‑8 (IL‑8) expression induced by Helicobacter pylori LPS in gastric cancer (GC) cells. Cells were treated with 200 ng/ml H. pylori‑LPS in the presence or absence of ebselen for various durations and concentrations (µmol/l). The expression of toll‑like receptor 4 (TLR4), GPX2, GPX4, p38 mitogen‑activated protein kinase (p38 MAPK), phosphorylated‑p38 MAPK, ROS production and IL‑8 expression were detected with western blotting or ELISA. The present study revealed that TLR4 expression was upregulated; however, GPX2 and GPX4 expression was reduced following treatment with H. pylori LPS, which led to increased ROS production, subsequently altering the IL‑8 expression level in GC cells. Additionally, it was determined that ebselen prevented the reduction in GPX2/4 levels induced by H. pylori LPS, however, TLR4 expression was not affected. Ebselen may also block the expression of IL‑8 by inhibiting phosphorylation of p38 MAPK. These data suggest ebselen may inhibit ROS production triggered by H. pylori LPS treatment via GPX2/4 instead of TLR4 signaling and reduce phosphorylation of p38 MAPK, resulting in altered production of IL‑8. Ebselen may, therefore, be a potential therapeutic agent to mediate H. pylori LPS-induced cell damage.
依布硒啉是一种有机硒化合物，具有抗氧化和抗炎特性。先前的研究表明，依布硒啉可抑制吸入性脂多糖（LPS）诱导的气道炎症，但其潜在的分子机制仍有待阐明。本研究探讨了依布硒啉对幽门螺杆菌 LPS 诱导的胃癌（GC）细胞谷胱甘肽过氧化物酶（GPX）-活性氧（ROS）途径和白细胞介素-8（IL-8）表达的影响。用 200ng/ml 幽门螺杆菌 LPS 及不同浓度（µmol/L）的依布硒啉处理细胞。用 Western blot 或 ELISA 检测 TLR4、GPX2、GPX4、p38 丝裂原激活蛋白激酶（p38 MAPK）、磷酸化 p38 MAPK、ROS 生成和 IL-8 表达。本研究显示，TLR4 表达上调；然而，幽门螺杆菌 LPS 处理后 GPX2 和 GPX4 表达降低，导致 ROS 生成增加，进而改变 GC 细胞中 IL-8 的表达水平。此外，研究发现依布硒啉可防止幽门螺杆菌 LPS 诱导的 GPX2/4 水平降低，但 TLR4 表达不受影响。依布硒啉还可能通过抑制 p38 MAPK 的磷酸化来抑制 IL-8 的表达。这些数据表明，依布硒啉可能通过 GPX2/4 而不是 TLR4 信号抑制幽门螺杆菌 LPS 治疗引发的 ROS 生成，并减少 p38 MAPK 的磷酸化，从而改变 IL-8 的产生。因此，依布硒啉可能是一种潜在的治疗剂，可介导幽门螺杆菌 LPS 诱导的细胞损伤。
