AIM： To investigate the presence of the cag-pathogenicity island and the associated histological damage caused by strains with complete cag-PAI and with partial deletions in correlation to the disease status. METHODS...AIM： To investigate the presence of the cag-pathogenicity island and the associated histological damage caused by strains with complete cag-PAI and with partial deletions in correlation to the disease status. METHODS： We analyzed the complete cag-PAI of 174 representative Helicobacter pylori （H pylori ） clinical isolates obtained from patients with duodenal ulcer, gastric ulcer, gastric cancer, and non-ulcer dyspepsia using eight different oligonucleotide primers viz cagA1, cagA2, cagAP1, cagAP2, cagE, cagT, LEC-1, LEC-2 spanning five different loci of the whole cag-PAI by polymerase chain reaction （PCR）. RESULTS： The complete screening of the genes comprising the cag-PAI showed that larger proportions of subjects with gastric ulcer （97.8%） inhabited strains with complete cag-PAI, followed by gastric cancer （85.7%）, non-ulcer dyspepsia （7.1%）, and duodenal ulcer （6.9%）, significant differences were found in the percentage distribution of the genes in all the clinical groups studied. It was found that strains with complete cag-PAI were able to cause severe histological damage than with the partially deleted ones. CONCLUSION： The cag-PAI is a strong virulent marker in the disease pathogenesis as it is shown that a large number of those infected with strain with complete cag-PAI had one or the other of the irreversible gastric pathologies and interestingly 18.5% of them developed gastric carcinoma. The presence of an intact cag- PAI correlates with the development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease. Partial deletions of the cag-PAI appear to be sufficient to render the organism less pathogenic.展开更多
AIM： To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Helicobacter pylori （H pylon） as a model of Hpylori-infected gastric epithelium, and to further examine the contribut...AIM： To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Helicobacter pylori （H pylon） as a model of Hpylori-infected gastric epithelium, and to further examine the contribution of cag-pathogenicity islands （cagPAI）-coding type IV secretion system and the two pathways, nuclear factor kappa B （NF-κB） and extracellular signal-regulated kinases （ERK） on wild-type Hpylori-induced gene expression. METHODS： Gene expression profiles induced by Hpylori were evaluated in AGS gastric epithelial cells using cDNA microarray, which were present in the 4600 independent clones picked up from the human gastric tissue. We also analyzed the contribution of NF-κB and ERK signaling on H pylori-induced gene expression by using inhibitors of specific signal pathways. The isogenic mutant with disrupted cagE （△cagE） was used to elucidate the role of cagPAI-encoding type IV secretion system in the gene expression profile. RESULTS： According to the expression profile, the genes were classified into four clusters. Among them, the clusters characterized by continuous upregulation were most conspicuous, and it contained many signal transducer activity-associated genes. The role of cagPAI on cultured cells was also investigated using isogenic mutant cagE, which carries non-functional cagPAI. Then the upregulation of more than 80% of the induced genes （476/566） was found to depend on cagPAI. Signal transducer pathway through NF-κB or ERK are the major pathways which are known to be activated by cagPAI-positive H pylori. The role of these pathways in the whole signal activation by cagPAI-positive H pyloriwas analyzed. The specific inhibitors against NF-κB or ERK pathway blocked the activation of gene expression in 65% （367/566） or 76% （429/566） of the genes whose activation appealed to depend on cagPAI. CONCLUSION： These results suggest that more than half of the genes induced by cayPAI-positive H pylori depend on NF-κB and ERK signaling activation, and these pathways may play a role in the gene expression induced by hostbacterial interaction which may associate with H pylorirelated gastro-duodenal diseases.展开更多
基金Supported by the Department of Biotechnology, Government of India , NO. BT/PR2473/Med/13/106/2001
文摘AIM： To investigate the presence of the cag-pathogenicity island and the associated histological damage caused by strains with complete cag-PAI and with partial deletions in correlation to the disease status. METHODS： We analyzed the complete cag-PAI of 174 representative Helicobacter pylori （H pylori ） clinical isolates obtained from patients with duodenal ulcer, gastric ulcer, gastric cancer, and non-ulcer dyspepsia using eight different oligonucleotide primers viz cagA1, cagA2, cagAP1, cagAP2, cagE, cagT, LEC-1, LEC-2 spanning five different loci of the whole cag-PAI by polymerase chain reaction （PCR）. RESULTS： The complete screening of the genes comprising the cag-PAI showed that larger proportions of subjects with gastric ulcer （97.8%） inhabited strains with complete cag-PAI, followed by gastric cancer （85.7%）, non-ulcer dyspepsia （7.1%）, and duodenal ulcer （6.9%）, significant differences were found in the percentage distribution of the genes in all the clinical groups studied. It was found that strains with complete cag-PAI were able to cause severe histological damage than with the partially deleted ones. CONCLUSION： The cag-PAI is a strong virulent marker in the disease pathogenesis as it is shown that a large number of those infected with strain with complete cag-PAI had one or the other of the irreversible gastric pathologies and interestingly 18.5% of them developed gastric carcinoma. The presence of an intact cag- PAI correlates with the development of more severe pathology, and such strains were found more frequently in patients with severe gastroduodenal disease. Partial deletions of the cag-PAI appear to be sufficient to render the organism less pathogenic.
基金Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sport, and Culture of Japan
文摘AIM： To elucidate the sequential gene expression profile in AGS cells co-cultured with wild-type Helicobacter pylori （H pylon） as a model of Hpylori-infected gastric epithelium, and to further examine the contribution of cag-pathogenicity islands （cagPAI）-coding type IV secretion system and the two pathways, nuclear factor kappa B （NF-κB） and extracellular signal-regulated kinases （ERK） on wild-type Hpylori-induced gene expression. METHODS： Gene expression profiles induced by Hpylori were evaluated in AGS gastric epithelial cells using cDNA microarray, which were present in the 4600 independent clones picked up from the human gastric tissue. We also analyzed the contribution of NF-κB and ERK signaling on H pylori-induced gene expression by using inhibitors of specific signal pathways. The isogenic mutant with disrupted cagE （△cagE） was used to elucidate the role of cagPAI-encoding type IV secretion system in the gene expression profile. RESULTS： According to the expression profile, the genes were classified into four clusters. Among them, the clusters characterized by continuous upregulation were most conspicuous, and it contained many signal transducer activity-associated genes. The role of cagPAI on cultured cells was also investigated using isogenic mutant cagE, which carries non-functional cagPAI. Then the upregulation of more than 80% of the induced genes （476/566） was found to depend on cagPAI. Signal transducer pathway through NF-κB or ERK are the major pathways which are known to be activated by cagPAI-positive H pylori. The role of these pathways in the whole signal activation by cagPAI-positive H pyloriwas analyzed. The specific inhibitors against NF-κB or ERK pathway blocked the activation of gene expression in 65% （367/566） or 76% （429/566） of the genes whose activation appealed to depend on cagPAI. CONCLUSION： These results suggest that more than half of the genes induced by cayPAI-positive H pylori depend on NF-κB and ERK signaling activation, and these pathways may play a role in the gene expression induced by hostbacterial interaction which may associate with H pylorirelated gastro-duodenal diseases.
