Assuntos
Hormônios Ectópicos/biossíntese , Hormônios Ectópicos/genética , Ileíte/etiologia , Ileíte/metabolismo , Íleo/metabolismo , Mediadores da Inflamação/metabolismo , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hormônios Ectópicos/fisiologia , Humanos , Ileíte/patologia , Íleo/patologia , Mediadores da Inflamação/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Camundongos TransgênicosRESUMO
Helicobacter pylori virulence factors have been suggested to be important in determining the outcome of infection. The H. pylori adhesion protein BabA2 is thought to play a crucial role in bacterial colonization and in induction of severe gastric inflammation, particularly in combination with expression of CagA and VacA. However, the influence of these virulence factors on the pathogenesis of H. pylori infection is still poorly understood. To address this question, the inflammatory gene expression profiles for two groups of patients infected with triple-negative strains (lacking expression of cagA, babA2, and vacAs1 but expressing vacAs2) and triple-positive strains (expressing cagA, vacAs1, and babA2 but lacking expression of vacAs2) were investigated. The gene expression patterns in the antrum gastric mucosa from patients infected with different H. pylori strains were very similar, and no differentially expressed genes could be identified by pairwise comparisons. Our data thus suggest that there is a lack of correlation between the host inflammatory responses in the gastric mucosa and expression of the babA2, cagA, and vacAs1 genes.
Assuntos
Citocinas/biossíntese , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/imunologia , Helicobacter pylori/fisiologia , Fatores de Virulência/biossíntese , Adesinas Bacterianas/biossíntese , Adesinas Bacterianas/genética , Adulto , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/genética , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Citocinas/genética , Perfilação da Expressão Gênica , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Humanos , Pessoa de Meia-Idade , Fatores de Virulência/genéticaRESUMO
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.