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-κB (NF-κB). We previously demonstrated that CagA interacts with host αPix. The present study was purposed to determine the role of the interaction of αPix 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 αPix- targeting siRNA. Activation of signalling molecules including p21-activated kinase (PAK), ERK and NF-κB, and expression of IL-8 in the cells were assessed. Results:H. pylori CagA was delivered into AGS cells and then interacted with αPix at 4 h following H. pylori infection. PAK1, ERK and NF-κB were activated in the cells containing NT and αPix siRNA at 12 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-κB were inhibited by down-regulation of αPix using siRNA but not by NT siRNA. The results indicate that αPix is required for H. pylori-mediated signalling of PAK1, ERK and NF-B. Additionally, Pix siRNA suppressed IL-8 induction after translocation of CagA into the cells, indicating that interaction of CagA with Pix is critical for CagA-mediating signalling for IL-8 expression. Conclusions. The interaction of αPix with CagA activates PAK1, ERK and NF-κB, which induces IL-8 expression in H. pylori-infected gastric epithelial cells.
Bibliographical noteFunding Information:
This work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-353-E00008) (to J. W. Lim) and a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean Government (MOST) (R11-2007-040-01002-0) (to H. Kim). H. Kim is grateful to the Brain Korea 21 Project, Yonsei University.
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