title: alphaPix interacts with Helicobacter pylori CagA to induce IL-8 expression in gastric epithelial cells.
abstract: 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-kappaB (NF-kappaB). We previously demonstrated that CagA interacts with host alphaPix. The present study was purposed to determine the role of the interaction of alphaPix with CagA on the signalling pathways for IL-8 expression in H. pylori-infected gastric epithelial cells.
  
  
  METHODS
  H. pylori HP99 strain (CagA+, VacA+) was infected to gastric epithelial AGS cells transfected with non-targeting (NT) or alphaPix- targeting siRNA. Activation of signalling molecules including p21-activated kinase (PAK), ERK and NF-kappaB, and expression of IL-8 in the cells were assessed.
  
  
  RESULTS
  H. pylori CagA was delivered into AGS cells and then interacted with alphaPix at 4 h following H. pylori infection. PAK1, ERK and NF-kappaB were activated in the cells containing NT and alphaPix 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-kappaB were inhibited by down-regulation of alphaPix using siRNA but not by NT siRNA. The results indicate that alphaPix is required for H. pylori-mediated signalling of PAK1, ERK and NF-kappaB. Additionally, alphaPix siRNA suppressed IL-8 induction after translocation of CagA into the cells, indicating that interaction of CagA with alphaPix is critical for CagA-mediating signalling for IL-8 expression.
  
  
  CONCLUSIONS
  The interaction of alphaPix with CagA activates PAK1, ERK and NF-kappaB, which induces IL-8 expression in H. pylori-infected gastric epithelial cells.
authors: Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors: Joo Weon
authors: JW
authors: Lim
authors: Kyung Hwan
authors: KH
authors: Kim
authors: Hyeyoung
authors: H
authors: Kim
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000096:biosynthesis; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000096:biosynthesis
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D020662:Guanine Nucleotide Exchange Factors; D016209:Interleukin-8; D016328:NF-kappa B; D064067:Rho Guanine Nucleotide Exchange Factors; C080866:cagA protein, Helicobacter pylori; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases