Inflammatory gene profiles in gastric mucosa during Helicobacter pylori infection in humans.
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.
Wen
Sicheng
S
Department of Laboratory Medicine, Karolinska Institute at Huddinge Hospital, Stockholm, Sweden.
Felley
Christian P
CP
Bouzourene
Hanifa
H
Reimers
Mark
M
Michetti
Pierre
P
Pan-Hammarström
Qiang
Q
D018829:Adhesins, Bacterial / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002908:Chronic Disease; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005838:Genotype; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011706:Pyloric Antrum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012737:Sex Factors
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; C400429:BabA protein, Helicobacter pylori; D001426:Bacterial Proteins; D002352:Carrier Proteins; D018836:Inflammation Mediators; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori