Nucleotide Binding Oligomerization Domain 1 Is an Essential Signal Transducer in Human Epithelial Cells Infected with Helicobacter pylori That Induces the Transepithelial Migration of Neutrophils

BACKGROUND/AIMS: The cytosolic host protein nucleotide binding oligomerization domain 1 (Nod1) has emerged as a key pathogen recognition molecule for innate immune responses in epithelial cells. The purpose of the study was to elucidate the mechanism by which Helicobacter pylori infection leads to transepithelial neutrophil migration in a Nod1-mediated manner. METHODS: Human epithelial cell lines AGS and Caco-2 were grown and infected with H. pylori. Interleukin (IL)-8 mRNA expression and IL-8 secretion were assessed, and nuclear factor kappaB (NF-kappaB) activation was determined. Stable transfections of AGS and Caco-2 cells with dominant negative Nod1 were generated. Neutrophil migration across the monolayer was quantified. RESULTS: Cytotoxin-associated gene pathogenicity island (cagPAI)(+) H. pylori infection upregulated IL-8 mRNA expression and IL-8 secretion in AGS and Caco-2 cells compared with controls. NF-kappaB activation, IL-8 mRNA expression and IL-8 secretion by cagPAI knockdown strains were reduced compared with those infected with the wild-type strain. NF-kappaB activation, IL-8 mRNA expression and IL-8 secretion in dominant-negative (DN)-Nod1 stably transfected cells were reduced compared with the controls. The transepithelial migration of neutrophils in DN-Nod1 stably transfected cells was reduced compared with that in controls. CONCLUSIONS: Signaling through Nod1 plays an essential role in neutrophil migration induced by the upregulated NF-kappaB activation and IL-8 expression in H. pylori-infected human epithelial cells.

Investigation of the association between clinical outcome and the cag pathogenicity-island and other virulence genes of Helicobacter pylori isolates from patients with dyspepsia in Eastern Turkey

The aims of our work were to determine the presence of the cag pathogenicity-island (cag PAI) and other virulence genes of Helicobacter pylori recovered from patients with gastritis and peptic ulcer, and to investigate the correlation of these virulence genes with clinical outcome. The presence of the cagA, the promoter regions of cagA, cagE, cagT, and the left end of cag-PAI (LEC), cag right junction (cagRJ), the plasticity region open reading frames (ORFs), vacA and oipA genes among 69 H. pylori isolates were determined by polymerase chain reaction. Intact cag PAI was detected in only one (1.4%) isolate. The cagA gene was identified in 52.1% and 76.2% of isolates from patients with dyspepsia (gastritis and peptic ulcer), respectively. The plasticity region ORFs i.e. JHP912 and JHP931 were predominantly detected in isolates from peptic ulcer. Less than 25% of the isolates carried other ORFs. Types I, II and III were the most commonly found among the isolates. None of the isolates possessed type Ib, 1c, IIIb, IV and V motifs. The most commonly vacA genotypes were s1am1a and s1m2 in isolates with peptic ulcer and gastritis, respectively. The results confirmed that the prevalence of oipA (Hp0638) gene was 75% and 85.7% in patients with gastritis and peptic ulcer, respectively. Furthermore, vacA s1am1a positivity was significantly related to peptic ulcer (p < 0.05).

Analysis of cag Pathogenicity Island of Helicobacter pylori Korean Isolate

It is commonly believed in the Western World that the more severe forms of gastroduodenal diseases like peptic ulcer are associated with infection by specific Helicobacter pylori strains classified as type I being considered to be more virulent than type II strains. However, in Korea, most of H. pylori isolates belong to type 1 strains regardless of virulence. Type I H. pylori strains differ from type II strains by the presence of the cag pathogenicity island (cag PAI) composed of a block of genes. In this study, the nucleotide sequence of cag PAI of the H. pylori Korean strain 51 was determined and compared with those of strains 26695 and J99 to assess the structural variation in the region and to evaluate its implication in the virulence of the H. pylori. The cag PAI of H. pylori strain 51 was smaller in size and in the number of constituting ORFs in comparison with 26695 and J99 strains. Although many cag orthologues were nearly identical one another with the similarity of 90% or more at the nucleotide and amino acid levels, there were some remarkable and significant differences in several cag genes among the three cag PAIs. Surprisingly, the percent similarities at amino acid level were lower than those at nucleotide level in one third of the ORFs. The two genes (cag7 and cagA) of strain 51 differed in sizes and deduced amino acid sequences from the corresponding genes of the other two strains. When comparing cagA ORF of H. pylori strain 51 with that of 8 non-Korean strains, phylogenetic tree revealed that the strain 51 formed a separate branch with the most far distances from the other strains except for a Japanese strain. The Cag7 protein of, strain 51 had a deletion in the repeat region II, suggesting a major change in the conformation and function of the protein.

The characteristic structure and classification of cag pathogenicity island in Chinese Helicobacter pylori strains / 中华消化杂志

0.05). The products of conjunction of cagⅠ and cagⅡ were found only in 5 strains. The detectable rate of continuous cag PAI was much higher in duodenal ulcer than in chronic gastritis ( P

Prevalence of cagA, cagE and cagT genes in cag pathogenicity island of Helicobacter pylori strains isolated from Shanghai patients and their clinical implications / 中华消化杂志

0.05). Of 98 cagE positive isolates, 14(14.3%) were cagA negative. Conclusion Most of the H. pylori isolates in Shanghai region may have intact cag PAI. cagE, could be taken as the marker for the presence of cag PAI. There is no correlation between the integrality of cag PAI and the clinical outcome of H. pylori of infection.

THE DISTRIBUTION AND SIGNIFICANCE OF cag Ⅰ IN HELICOBACTER PYLORI ISOLATED FROM CHINESE PATIENTS / 解放军医学杂志

To investigate the distrbution of cag Ⅰin Helicobacter pylori(Hp) isolated from Chinese patients, and its relationship to gastroduodenal diseases. Fragment in cag Ⅰ was amplified by polymerase chain reaction(PCR) in 107 Hp strains from Chinese patients. Results The amplicom to cag Ⅰ was positive in 93 strains, of which 57 strains came from patients with chronic gastritis, 31 strains from peptic ulcer, and 5 strains from gastric carcinoma.Conclusion Existance of cag Ⅰ of Hp strains was popular in the Chinese population, but no data had proven the relation ship between the existence of cag 1and occurrence of Hp related diseases and inflammatory infiltration in gastric mucosa.