Relationship of IL-8 production and the CagA status in AGS cells infected with Helicobacter pylori exposed to low pH and activating transcription factor 3 (ATF3)

Microbiol Res. 2009;164(2):180-90. doi: 10.1016/j.micres.2006.10.010. Epub 2007 Apr 20.


We examined the kinetics of IL-8 production and CagA status in AGS infected with Helicobacter pylori, 26695 (Western CagA-type), HPK5 (Eastern CagA-type) and isogenic cagA-disrupted mutants, exposed to different pH (pH 6 and pH 3). IL-8 was produced in the early and late phases after infection in CagA-dependent and -independent manners, respectively, irrespective of CagA-type. The wild-type exposed to low pH tremendously reduced IL-8 level at early phase, but restored with urea, suggesting that low pH exerted the kinetics of H. pylori-induced IL-8 production in CagA-dependent manner and urea was necessary for effective induction. CagA and phosphorylated CagA increased time-dependently after infection. Phosphorylated CagA from 26695, but not HPK5, rapidly peaked, consistent with the kinetics of IL-8 induction and appearance of hummingbird phenotype. ATF3 transcripts peaked late phase by wild-type, however, induced in two peaks early and late phases by cagA-disrupted mutants, indicating that different CagA-type proteins altered ATF3 induction in the infected cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / genetics*
  • Antigens, Bacterial / metabolism*
  • Bacterial Proteins / metabolism*
  • Cell Line, Tumor
  • Gene Expression
  • Helicobacter Infections / genetics
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / genetics
  • Helicobacter pylori / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Interleukin-8 / immunology*
  • Phosphorylation


  • ATF3 protein, human
  • Activating Transcription Factor 3
  • Antigens, Bacterial
  • Bacterial Proteins
  • Interleukin-8
  • cagA protein, Helicobacter pylori