alphaPix interacts with Helicobacter pylori CagA to induce IL-8 expression in gastric epithelial cells

摘要

Objective. Helicobacter pylori CagA, translocated into gastric epithelial cells, induces IL-8 expression through the signalling pathways, including extracellular signal-regulated kinase (ERK) and nuclear factor-KB (NF-kappaB). We previously demonstrated that CagA interacts with host aPix. The present study was purposed to determine the role of the interaction of aPix with CagA on the signalling pathways for IL-8 expression in H. pylori-infected gastric epithelial cells. Material and methods. H. pylori HP99 strain (CagA+, VacA+) was infected to gastric epithelial AGS cells transfected with non-targeting (NT) or aPix- targeting siRNA. Activation of signalling molecules including p21-activated kinase (PAK), ERK and NF-kB, and expression of IL-8 in the cells were assessed. Results. H. pylori CagA was delivered into AGS cells and then interacted with aPix at 4 h following H. pylori infection. PAK1, ERK and NF-kB were activated in the cells containing NT and aPix siRNA at 1-2 h following H. pylori infection. However, after 4 h, the time when CagA was delivered into the cells, the activations of PAK1, ERK and NF-kB were inhibited by down-regulation of aPix using siRNA but not by NT siRNA. The results indicate that aPix is required for H. pylori'-mediated signalling of PAK1, ERK and NF-kappaB. Additionally, aPix siRNA suppressed IL-8 induction after translocation of CagA into the cells, indicating that interaction of CagA with aPix is critical for CagA-mediating signalling for IL-8 expression. Conclusions. The interaction of aPix with CagA activates PAK1, ERK and NF-kB, which induces IL-8 expression in H. pylori-infected gastric epithelial cells.