Differential effects of multiplicity of infection on Helicobacter pylori-induced signaling pathways and interleukin-8 gene transcription

J Clin Immunol. 2011 Feb;31(1):60-8. doi: 10.1007/s10875-010-9467-5. Epub 2010 Oct 1.

Abstract

Interleukin-8 (IL-8) plays a central role in the pathogenesis of Helicobacter pylori infection. We used four different H. pylori strains isolated from patients with gastritis or duodenal ulcer disease to examine their differential effects on signaling pathways and IL-8 gene response in gastric epithelial cells. IL-8 mRNA level is elevated in response to high (100) multiplicity of infection (MOI) independent of cagA, vacA, and dupA gene characteristics. By lower MOIs (1 or 10), only cagA ( + ) strains significantly induce IL-8 gene expression. This is based on differential regulation of IL-8 promoter activity. Analysis of intracellular signaling pathways indicates that H. pylori clinical isolates induce IL-8 gene transcription through NF-κB p65, but by a MOI-dependent differential activation of MAPK pathways. Thus, the major virulence factors of H. pylori CagA, VacA, and DupA might play a minor role in the level of IL-8 gene response to a high bacterial load.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Load*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cell Line
  • Duodenal Ulcer / immunology
  • Duodenal Ulcer / microbiology
  • Duodenal Ulcer / physiopathology
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Gastritis / immunology
  • Gastritis / microbiology
  • Gastritis / physiopathology
  • Gene Expression Regulation*
  • Helicobacter Infections / immunology
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / classification
  • Helicobacter pylori / genetics
  • Helicobacter pylori / isolation & purification
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic / genetics
  • Signal Transduction*
  • Stomach / cytology
  • Stomach / immunology
  • Stomach / microbiology
  • Transcription, Genetic
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • Bacterial Proteins
  • Interleukin-8
  • NF-kappa B
  • Virulence Factors
  • Mitogen-Activated Protein Kinase Kinases