RESUMO
The gastric pathogen Helicobacter pylori activates epithelial cell signaling pathways, and its infection induces changes in the expression of several genes in infected human gastric tissues. Recent studies have indicated that the ability of H. pylori to regulate epithelial cell responses depends on the presence of an intact cag pathogenicity island (cagPAI). We investigated altered mRNA expression of gastric epithelial cells after infection with H. pylori, both cagPAI-positive and cagPAI-negative strains, by cDNA microarray, reverse transcription PCR, and Northern blot analysis. Our results indicated that cagPAI-positive H. pylori strains (ATCC 43504 and clinical isolated strains) significantly activated Smad5 mRNA expression of human gastric epithelial cells (AGS, KATOIII, MKN28, and MKN45). We further examined whether the up-regulated Smad5 was related to apoptosis of gastric epithelial cells induced by H. pylori. Smad5 RNA interference completely inhibited H. pylori-induced apoptosis. These results suggest that Smad5 is up-regulated in gastric epithelial cells through the presence of cagPAI of H. pylori and that Smad5 mediates apoptosis of gastric epithelial cells induced by H. pylori infection.
Assuntos
Apoptose , Proteínas de Ligação a DNA/biossíntese , Mucosa Gástrica/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Fosfoproteínas/biossíntese , Transativadores/biossíntese , Linhagem Celular , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/metabolismo , Humanos , Transdução de Sinais , Proteína Smad5 , Regulação para CimaAssuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Úlcera Péptica/epidemiologia , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Dispepsia/epidemiologia , Dispepsia/etiologia , Feminino , Seguimentos , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/etiologia , Qualidade de Vida , Recidiva , Inquéritos e Questionários , Fatores de TempoRESUMO
BACKGROUND: The cag pathogenicity island (cag PAI) is a major virulence factor. The ability of Helicobacter pylori to adhere to gastric epithelial cells is an important initial step for virulence. The aim of this study was to evaluate the relationship between genetic variations of cag PAI in Japanese clinical isolates and the ability of H. pylori to adhere to gastric epithelial cells. MATERIALS AND METHODS: The polymerase chain reaction and Southern blot analysis were used to verify the presence or absence of cagA, cagE, cagG, cagI and cagM in the cag PAI in 236 Japanese clinical isolates. The ability of H. pylori to adhere to KATOIII cells was examined by flow cytometry. RESULTS: Seven (3.0%) cag PAI partial-deleted strains were found in 236 clinical isolates, and these strains showed three patterns in the deleted region within the cag PAI. All of the cagG-deleted strains showed decreased adherence to KATOIII cells, in comparison with cagG-positive strains. These strains had abolished IL-8 induction despite the presence of cagE, which is essential for IL-8 induction. CONCLUSIONS: Our results suggest that cagG or surrounding genes in the cag PAI has a function related to adhesion to epithelial cells.
