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

Authors
 JOO WEON LIM  ;  KYUNG HWAN KIM  ;  HYEYOUNG KIM 
Citation
 SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, Vol.44(10) : 1166-1172, 2009 
Journal Title
 SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY 
ISSN
 0036-5521 
Issue Date
2009
MeSH
Antigens, Bacterial/metabolism* ; Bacterial Proteins/metabolism* ; Epithelial Cells/metabolism* ; Epithelial Cells/microbiology ; Extracellular Signal-Regulated MAP Kinases/biosynthesis ; Guanine Nucleotide Exchange Factors/metabolism* ; Helicobacter Infections/metabolism* ; Humans ; Interleukin-8/biosynthesis* ; NF-kappa B/biosynthesis ; Rho Guanine Nucleotide Exchange Factors ; Signal Transduction ; Stomach/metabolism* ; p21-Activated Kinases/biosynthesis
Keywords
αPix ; CagA ; gastric epithelial cells ; Helicobacter pylori ; IL-8
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. MATERIAL AND 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.
Full Text
http://informahealthcare.com/doi/abs/10.1080/00365520903144398
DOI
10.1080/00365520903144398
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105117
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