Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ5-integrin-integrin linked kinase signalling complex

Objective One of the most important hormones in the human stomach is the peptide gastrin. It is mainly required for the regulation of gastric pH but is also involved in growth and differentiation of gastric epithelial cells. In Helicobacter pylori infected patients, gastrin secretion can be upregulated by the pathogen, resulting in hypergastrinaemia. H pylori induced hypergastrinaemia is described as being a major risk factor for the development of gastric adenocarcinoma. Design In this study, the upstream receptor complex and bacterial factors involved in H pylori induced gastrin gene expression were investigated, utilising gastric epithelial cells which were stably transfected with a human gastrin promoter luciferase reporter construct. Results Integrin linked kinase (ILK) and integrin beta 5, but not integrin beta 1, played an important role in gastrin promoter activation. Interestingly, a novel CagL/integrin beta 5/ILK signalling complex was characterised as being important for H pylori induced gastrin expression. On interaction of H pylori with alpha v beta(5)-integrin and ILK, the epidermal growth factor receptor (EGFR) -> Raf -> mitogen activated protein kinase kinase (MEK) -> extracellular signal regulated kinase (Erk) downstream signalling cascade was identified which plays a central role in H pylori gastrin induction. Conclusion The newly discovered recognition receptor complex could be a useful target in treating precancerous conditions triggered by H pylori induced hypergastrinaemia.