cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori epithelial cell response genes

Helicobacter pylori strains containing the cag pathogenicity island (PAI) i nduce NF-kappaB activation and interleukin-8 secretion in gastric epithelia l cells. The aim of this study was to investigate changes in epithelial gen e expression induced by cag PAI-positive and -negative strains of H. pylori using high-density cDNA array hybridization technology. Radio-labeled cDNA prepared from H. pylori-infected Kato 3 gastric epithelial cells was hybri dized to high-density cDNA arrays to identify changes in epithelial gene ex pression compared to noninfected controls. In vivo expression of selected, differentially expressed genes was examined by reverse transcription-PCR an alysis of H. pylori-positive and -negative gastric mucosa. Screening of ca. 57,800 cDNAs identified 208 known genes and 48 novel genes and/or expresse d sequence tags of unknown function to be differentially expressed in Kato 3 cells following H. pylori infection. Marked differences in gene expressio n profiles were observed following cag PAI-positive and cag PAI-negative in fection with 15 novel cDNAs and 92 known genes being differentially express ed. H. pylori was found to change the expression of genes encoding growth f actors and cytokine/chemokines and their receptors, apoptosis proteins, tra nscription factors and metalloprotease-disintegrin proteins (ADAMs), and ti ssue inhibitors of metalloproteinases. Gastric differential expression of s elected known genes (amphiregulin and ADAM 10) and a novel gene (HPYR1) was confirmed in vivo in patients with H. pylori infection. Confirmation of th e in vivo expression of selected genes demonstrates the usefulness of this approach for investigating pathogen-induced changes in host gene expression .