HELICOBACTER-PYLORI CULTURE SUPERNATANT INTERFERES WITH EPIDERMAL GROWTH FACTOR-ACTIVATED SIGNAL-TRANSDUCTION IN HUMAN GASTRIC KATO-III CELLS

The mechanisms by which Helicobacter pylori infection leads to gastrod uodenal ulceration remain poorly understood. Previous studies have sho wn that H. pylori vacuolating cytotoxin (VacA) inhibits proliferation of gastric epithelial cells, which suggests that H. pylori may interfe re with gastric mucosal repair mechanisms. In this study, we investiga ted the effects of H. pylori broth culture supernatants on epidermal g rowth factor (EGF)-mediated signal transduction pathways in a gastric carcinoma cell Line (KATO III). Exposure of these cells to EGF resulte d in increased expression and phosphorylation of the EGF receptor (EGF -R), increased ERK2 activity and phosphorylation, and increased c-fos protein levels. Preincubation of cells with broth culture supernatant from VacA (+) H. pylori strain 60190 inhibited the capacity of EGF to induce each of these effects. In contrast, pre incubation of cells wit h broth culture supernatant from an isogenic VacA-mutant strain (H. py lori 60190-v1) failed to inhibit the effects of EGF. These results sug gest that the H. pylori vacuolating cytotoxin interferes with EGF-acti vated signal transduction pathways, which are known to be essential fo r cell proliferation and ulcer healing.