Protective effect of rebamipide against Helicobacter pylori-CagA-induced effects on gastric epithelial cells

Dig Dis Sci. 2011 Feb;56(2):441-8. doi: 10.1007/s10620-010-1299-x. Epub 2010 Jun 16.

Abstract

Background: Helicobacter pylori CagA dysregulates cell signaling pathways and leads to targeted transcriptional up-regulation of genes implicated in gastric cell injury. The aim of this study was to determine the effects of rebamipide on CagA-induced effects on gastric epithelial cells. We investigated the effects of rebamipide treatment (pre- or post-treatment before or after CagA transfection) on CagA-induced gastric cell injury.

Method: We evaluated the morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization by confocal microscopy, IL-8 production by ELISA, and NF-κB activation by luciferase assay in AGS gastric epithelial cells and MDCK cells.

Results: Transfection of CagA into gastric epithelial cells induced morphologic changes (hummingbird phenotype), ZO-1 mislocalization, and IL-8 production in gastric epithelial cells. Pre-treatment with rebamipide inhibits CagA-induced effects on gastric epithelial cells, including morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization, IL-8 production, and NF-κB activity.

Conclusions: These results suggest that rebamipide might have a potential role in the protection of H. pylori CagA-induced effects on gastric epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / pharmacology
  • Animals
  • Anti-Ulcer Agents / pharmacology
  • Antigens, Bacterial / toxicity*
  • Antioxidants / pharmacology*
  • Bacterial Proteins / toxicity*
  • Cell Line
  • Dogs
  • Epithelial Cells / drug effects*
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Quinolones / pharmacology*
  • Stomach / cytology*
  • Stomach / drug effects
  • Time Factors
  • Zonula Occludens-1 Protein

Substances

  • Anti-Ulcer Agents
  • Antigens, Bacterial
  • Antioxidants
  • Bacterial Proteins
  • Interleukin-8
  • Membrane Proteins
  • NF-kappa B
  • Phosphoproteins
  • Quinolones
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • cagA protein, Helicobacter pylori
  • rebamipide
  • Alanine