Regulation of Helicobacter pylori-induced Interleukin-8 Production by Gastric Epithelial Cells in vitro

Lee, Yong Chan; Kim, Won Ho; Lee, Han Young; Moon, Young Myung; Kang, Jin Kyung; Park, In Suh

Abstract

BACKGROUND/AIMS: Production of interleukin-8 (IL-8) by gastric epithelial cells may play an impor tant role in H. pylori-induced mucosal injury. The aim of this study was to evaluate physico-chemica factors and signal pathway regulating H. pylori-induced IL-8 production.
METHODS
Various physica and chemical pretreatments of H. pylori were performed before the stimulation of gastric epithelia cells such as AGS and KATO III. After pretreatment with protein kinase inhibitors, the production of IL-8 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively. To evaluate the possible synergism of tumor ne crosis factor (TNF) secreted by epithelial cells, the pretreatment with anti-TNF blocking antibody was performed.
RESULTS
Significant decrease in IL-8 production was noted when H. pylori was pretreated with various physical and chemical methods. H89 (10 microM) and calyculin A (25 nM) had no effec on IL-8 production, while staurosporin (1 microM), herbimycin A (40 nM) or genistein (250 microM significantly inhibited the IL-8 production by epithelial cells. The IL-8 production induced by TNF and H. pylori was also inhibited by protein tyrosine kinase (PTK) inhibitors and protein kinase C (PKC) inhibitors. Anti-TNF antibody showed no significant effect on the H. pylori-induced IL-8 production.
CONCLUSIONS
A live bacterium adhering to epithelial cell induces IL-8 production by epithelial cells. Two different protein kinases (PTK and PKC) may be involved in H. pylori-induced IL-8 production of epithelial cells.