Transcriptional regulation by thiol compounds in Helicobacter pylori-induced IL-8 production in human gastric epithelial cells

Abstract

Reactive oxygen species (ROS) have been counted among the potential toxic factors involving Helicobacter pylori (H. pylori)-induced gastric injury. Transcription nuclear factor-κB (NF-κB) is activated by ROS and regulates inflammatory gene expression. Thiol compounds, such as glutathione and N-acetylcysteine, scavenge hydrogen peroxide and are reported to prevent oxidative damage in various cells. The present study aims to investigate whether thiol compounds could affect H. pylori-induced IL-8 production by regulating transcription factor NF-κB in human gastric epithelial AGS cells. AGS cells were incubated with H. pylori (NCTC 11637) at a ratio of 1:100 in the presence or absence of thiol compounds. ROS generation was determined by confocal microscopy using ROS-sensitive dichlorofluorescein diacetate dye. Levels of hydrogen peroxide and IL-8 in the medium and DNA binding activity of NF-κB were determined by enzyme-linked immunosorbent assay, colorimetric assay, and electrophoretic mobility shift assay. Results indicated both thiol compounds inhibited H. pylori-induced hydrogen peroxide production, in accordance with their inhibition on NF-κB activation and IL-8 production induced by H. pylori in AGS cells. In conclusion, ROS may be a signaling molecule triggering NF-κB activation and the expression of inflammatory genes such as IL-8.