Helicobacter pylori infection induced alteration of gene expression in human gastric cells

Background-Helicobacter pylori, a human pathogen responsible for many diges tive disorders, induces complex changes in patterns of gene expression in i nfected tissues. cDNA expression arrays provide a useful tool for studying these complex phenomena. Aim-To identify genes that showed altered expression after H pylori infecti on of human gastric cells compared with uninfected controls. Methods-The gastric adenocarcinoma cell line AGS was cocultivated with PI p ylori. Growth of infected cells was determined by trypan blue exclusion ass ay. Complementary DNA probes derived from H pylori treated and untreated ce lls were hybridised to two identical Atlas human cDNA expression arrays, an d those genes with altered expression levels were identified. A real time q uantitative reverse transcription-polymerase chain reaction assay was used to better define expression patterns of these genes in endoscopically gastr ic mucosal biopsies with and without H pylori infection. Results-Over 24 hours, coincubation with H pylori inhibited AGS cell growth but did not cause a noticeable degree of cell death. H pylori treatment al tered the pattern of gene expression in AGS cells. We identified 21 overexp ressed genes and 17 suppressed genes from the cDNA expression arrays. The m ajority of genes were transcription factors such as c-jun, BTEB2, and ETR10 1. Other genes were involved in signal transduction pathways, such as MAP k inase, interleukin 5, and insulin-like growth factor. Genes involved in cel l cycle regulation and differentiation, such as CDC25B and NM23-H2, were al so identified. In patients with H pylori infection (n=20), there was a sign ificant difference for ERCC3, Id-2, and NM23-H2 mRNA levels in infected gas tric mucosa. compared with uninfected gastric mucosa in patients without pe ptic diseases (n=20) (ERCC3 4.75 molecules/10(4) beta -actin mRNA molecules v 13.65, p<0.001; Id-2 16.1 v 23.4, p<0.05; NM23-H2 17.5 v 45.5, p<0.001). There was no significant difference between mRNA levels of c-jun and CDC25 B in H pylori colonised gastric mucosa and uninfected mucosa. Conclusion-We demonstrated that H pylori infection caused alteration of gen e expression in AGS cells. The differential hybridisation technique of Atla s human cDNA expression array is a useful method to identify host genes inv olved in patho genic mechanisms in H pylori infection.