AI-2 Represses CagA Expression and Bacterial Adhesion, Attenuating the Helicobacter Pylori-Induced Inflammatory Response of Gastric Epithelial Cells.

Background Helicobacter pylori (H. pylori) infection of gastric epithelial cells induces inflammatory response. Outer membrane proteins (OMPs), Type 4 secretion system (T4SS) encoded by cagPAI, and the effector protein CagA are involved in the pathogenesis of H. pylori. H. pylori possesses a gene encoding LuxS which synthesizes AI-2, a quorum sensing signal molecule. The aim of this study was to investigate the role of AI-2 in the expression of virulence factors and the inflammatory response of gastric epithelial (AGS) cells induced by H. pylori. Materials and Methods H. pylori Delta luxS mutant was constructed, and AI-2 activity was measured with Vibrio harveyi BB170. NF-kappa B activation, IL-8 production, expression of OMPs (outer membrane proteins), CagA, and T4SS encoded by cagPAI were investigated in H. pylori wild type, and Delta luxS with or without supplementation of AI-2. Results H. pylori produced approximately 7 mu M of AI-2 in the medium. AI-2 inhibited expression and translocation of CagA after infection of AGS cells. AI-2 upregulated the expression of CagM, CagE, and CagX, while had no effect to the interaction between T4SS and alpha 5 beta 1 integrin. AI-2 also reduced expression of adhesins and bacterial adhesion to AGS cells. Finally, AI-2 reduced the activation of NF-kappa B and expression of IL-8 in H. pylori-infected AGS. Conclusions AI-2 plays an important role in the pathogenesis of H. pylori. AI-2 inhibits the bacterial adhesion, expression, and translocation of CagA, and attenuates the inflammatory response of AGS cells induced by H. pylori.