AI‐2 represses CagA expression and bacterial adhesion, attenuating the Helicobacter pylori‐induced inflammatory response of gastric epithelial cells

Abstract Background Helicobacter pylori ( H. pylori ) infection of gastric epithelial cells induces inflammatory response. Outer membrane proteins (OMPs), Type 4 secretion system (T4SS) encoded by cag PAI, 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 Δ luxS mutant was constructed, and AI‐2 activity was measured with Vibrio harveyi BB170. NF‐κB activation, IL‐8 production, expression of OMPs (outer membrane proteins), CagA, and T4SS encoded by cag PAI were investigated in H. pylori wild type, and Δ luxS with or without supplementation of AI‐2. Results H. pylori produced approximately 7 μM 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 α5β1 integrin. AI‐2 also reduced expression of adhesins and bacterial adhesion to AGS cells. Finally, AI‐2 reduced the activation of NF‐κB 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 .