Inflammatory Gene Profiles in Gastric Mucosa during Helicobacter pylori Infection in Humans

Abstract

Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, ultimately leading to cellular hyperproliferation and malignant transformation. Hitherto, only expression of a single gene, or a limited number of genes, has been investigated in infected patients. cDNA arrays were therefore used to establish the global pattern of gene expression in gastric tissue of healthy subjects and of H. pylori-infected patients. Two main gene expression profiles were identified based on cluster analysis. The data obtained suggest a strong involvement of selected Toll-like receptors, adhesion molecules, chemokines, and ILs in the mucosal response. This pattern is clearly different from that observed using gastric epithelial cell lines infected in vitro with H. pylori. The presence of a “Helicobacter-infection signature,” i.e., a set of genes that are up-regulated in biopsies from H. pylori-infected patients, could be derived from this analysis. The genotype of the bacteria (presence of genes encoding cytotoxin-associated Ag, vacuolating cytotoxin, and blood group Ag-binding adhesin) was analyzed by PCR and shown to be associated with differential expression of a subset of genes, but not the general gene expression pattern. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Future studies may help identify gene expression patterns predictive of complications of the infection.

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

“…2,9 Our work identifies for the first time a limited set of molecules (GATA6, STAT6, MMP7, CXCL13, UBD, MAPK8, LY96, WFDC2) that establish a risk associated with H. pylori infection. Our study performed on a large number of H. pylori-infected patients has provided new insights into the cellular host responses to H. pylori infection and suggests that a premalignant molecular signature can be detected in the most severely infected cases, before any histological evidence of malignancy.…”

“…8 Very few analyses have been performed in human tissue infected by H. pylori 9,27 and reported studies have included only few distinct tissue samples. The heterogeneity of tissue origin and nature of the samples (ie, whole gastric mucosa or biopsies), as well as uncertainties about patients' status (chronic active gastritis with or without metaplasia or atrophy), underscore the need for more standardized studies.…”

“…The heterogeneity of tissue origin and nature of the samples (ie, whole gastric mucosa or biopsies), as well as uncertainties about patients' status (chronic active gastritis with or without metaplasia or atrophy), underscore the need for more standardized studies. 9,27 Our present study was carried out on both antral and fundic biopsies from a large series of patients with 'homogeneous' epidemiological, clinical, and histological data.…”

“…7,8 DNA microarray technologies have also been employed to profile human tissue infected by H. pylori. 9 However, this latter study was performed on a limited number of patients and potential protein alterations were not confirmed by immunohistochemical staining of affected tissue.…”

Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology

“…35,36,40,42,43 A set of proinflammatory chemokines has been shown to be involved in H. pylori gastritis: Gro-a, IL-8, RANTES, IFN-c-inducible protein-10 (CXCL10), a monokine induced by IFN-c (CXCL11) and CCL20 (MIP-3a/LARC/exodus). 15,[44][45][46] It has been demonstrated that the gastrointestinal epithelium senses the invading microorganisms and produces cytokines/chemokines that attract lymphocytes and dendritic cells to the site of inflammation. 35,47,48 Recently, it was reported that CCR6 mediates dendritic cell localization, lymphocyte homeostasis and immune responses in mucosal tissue.…”