The effects of cure of Helicobacter pylori infection on the signal transduction of gastric epithelial cells

Aliment Pharmacol Ther. 2003 Jul:18 Suppl 1:39-44. doi: 10.1046/j.1365-2036.18.s1.2.x.

Abstract

Background: The CagA protein of Helicobacter pylori is directly injected from the bacteria into cells via the bacterial type IV secretion system and undergoes tyrosine phosphorylation in the gastric epithelial cells. Translocated CagA forms a physical complex with the SRC homology 2 domain (SH2)-containing tyrosine phosphatase SHP-2, which plays an important role in mitogenic signal transduction in the host cells.

Aim: We examined the effect of eradication therapy on the signal transduction pathway of gastric epithelial cells induced by the CagA protein of H. pylori.

Methods: Gastric biopsy samples were obtained from 20 H. pylori-positive atrophic gastritis patients before, and 3 months after, H. pylori infection eradication therapy, and subjected to immunoblot analysis to detect tyrosine phosphorylated CagA protein and CagA co-immunoprecipitated endogenous SHP-2.

Results: Tyrosine phosphorylated CagA protein and CagA co-immunoprecipitated endogenous SHP-2 were detected in the gastric mucosa from H. pylori-positive atrophic gastritis patients. All H. pylori strains from these patients were cagA-positive type I strains. After curing H. pylori infection, the tyrosine phosphorylated CagA protein and CagA co-immunoprecipitated endogenous SHP-2 disappeared from the gastric mucosa.

Conclusion: The cure of infection reduces the stimulated signal transduction of gastric epithelial cells by the translocated CagA protein of H. pylori, and may confer a beneficial effect on the reduction of cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • DNA-Binding Proteins*
  • Drosophila Proteins*
  • Epithelial Cells
  • Female
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / therapy*
  • Helicobacter pylori*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Phosphorylation
  • Polymerase Chain Reaction / methods
  • Precipitin Tests
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases / metabolism*
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Transcription Factors
  • Trl protein, Drosophila
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases