Helicobacter pylori Culture Supernatant Inhibits Binding and Proliferative Response of Human Gastric Cells to Epidermal Growth Factor: Implications for H. pylori Interference with Ulcer Healing?

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Abstract
Helicobacter pylori (H. pylori) infection of gastric mucosa is strongly associated with gastritis and peptic ulcer disease. However, the mechanisms of the ulcerogenic action of H pylori and/or the interference of H pylori with ulcer healing are unknown. Through binding to its receptor, epidermal growth factor (EGF) accelerates cells migration and triggers epithelial cell proliferation which are both important for the healing of gastroduodenal ulcers. H pylori seems to interfere with ulcer healing, but the cellular and molecular targets and mechanisms of these actions have not been elucidated. In the present study, we tested the effect of H. pylori culture supernatant (dialyzed to remove molecules smaller than 10 kD) on EGF binding to its receptor and on the proliferative response of human gastric Kato III cells to EGF. H. pylori culture supernatant significantly reduced specific binding of EGF to its receptor and reduced EGF-stimulated gastric cell proliferation. Since ulcer healing requires epithelial cell proliferation and cell migration (re-epithelialization), which are both triggered by EGF binding to its receptor, the alteration in these mechanisms by H. pylori product may be the basis of H. pylori-induced interference with ulcer healing.

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