Transcriptional regulation by thiol compounds in Helicobacter pylori-induced interleukin-8 production in human gastric epithelial cells.
Reactive oxygen species (ROS) have been counted among the potential toxic factors involving Helicobacter pylori (H. pylori)-induced gastric injury. Transcription nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB 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-kappaB activation and IL-8 production induced by H. pylori in AGS cells. In conclusion, ROS may be a signaling molecule triggering NF-kappaB activation and the expression of inflammatory genes such as IL-8.
Seo
Jeong Yeon
JY
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Kim
Hyeyoung
H
Kim
Kyung Hwan
KH
D000111:Acetylcysteine / Q000494:pharmacology; D000230:Adenocarcinoma; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D005978:Glutathione / Q000494:pharmacology; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016209:Interleukin-8; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine