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).

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.