Limits...
H. pylori CagL-Y58/E59 prime higher integrin α5β1 in adverse pH condition to enhance hypochlorhydria vicious cycle for gastric carcinogenesis.

Yeh YC, Cheng HC, Yang HB, Chang WL, Sheu BS - PLoS ONE (2013)

Bottom Line: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk.Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks.In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05).

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

ABSTRACT

Background/aims: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis.

Methods: The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks.

Results: Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5β1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05).

Conclusions: H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication.

Show MeSH

Related in: MedlinePlus

Integrin α5 expression and CagA phosphorylation after H. pylori infection are pH dependent.(A) Integrin α5 and β1 expressions of AGS cells cultivated alone or co-cultivated with Hp1033 at pH 7.4, 5.4, and 4.4, respectively. Cell lysate was immunoblotted with an anti-integrin α5 and anti- integrin β1 antibody. GAPDH served as an internal control for sample normalization. The integrin α5 expression was significantly higher in trend-like fashion as the pH elevated from 4.4, 5.4, to 7.4 (*indicated p<0.05). (B) CagA phosphorylation of AGS cells co-cultivated with Hp1033 for 8 h at pH 7.4, 5.4 and 4.4, respectively. Cell lysate was immunoblotted with an anti-CagA, Hsp60 and anti-phospho-CagA antibody. The CagA phosphorylation at pH 5.4 was higher than that of pH 4.4 (p<0.05). The data are shown as mean value ± standard deviation of the triplicate experiments.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3757014&req=5

pone-0072735-g001: Integrin α5 expression and CagA phosphorylation after H. pylori infection are pH dependent.(A) Integrin α5 and β1 expressions of AGS cells cultivated alone or co-cultivated with Hp1033 at pH 7.4, 5.4, and 4.4, respectively. Cell lysate was immunoblotted with an anti-integrin α5 and anti- integrin β1 antibody. GAPDH served as an internal control for sample normalization. The integrin α5 expression was significantly higher in trend-like fashion as the pH elevated from 4.4, 5.4, to 7.4 (*indicated p<0.05). (B) CagA phosphorylation of AGS cells co-cultivated with Hp1033 for 8 h at pH 7.4, 5.4 and 4.4, respectively. Cell lysate was immunoblotted with an anti-CagA, Hsp60 and anti-phospho-CagA antibody. The CagA phosphorylation at pH 5.4 was higher than that of pH 4.4 (p<0.05). The data are shown as mean value ± standard deviation of the triplicate experiments.

Mentions: In the absence of H. pylori infection, there were no differences in the integrin α5 and β1 expressions of AGS cells among different pH values at 7.4, 5.4, or 4.4 (Figure 1A). However, the integrin α5 expression, but not integrin β1 expression, was significantly increased in the AGS cells exposed to Hp1033 isolates, when the pH of the culture medium increased from 4.4 to 7.4 (p<0.05, Figure 1A). Moreover, as depicted in Figure 1B, the CagA phosphorylation of AGS cells co-cultivated with Hp1033 was lower at pH 4.4 than at either pH 7.4 or pH 5.4 (p = 0.08 or p<0.01, respectively).


H. pylori CagL-Y58/E59 prime higher integrin α5β1 in adverse pH condition to enhance hypochlorhydria vicious cycle for gastric carcinogenesis.

Yeh YC, Cheng HC, Yang HB, Chang WL, Sheu BS - PLoS ONE (2013)

Integrin α5 expression and CagA phosphorylation after H. pylori infection are pH dependent.(A) Integrin α5 and β1 expressions of AGS cells cultivated alone or co-cultivated with Hp1033 at pH 7.4, 5.4, and 4.4, respectively. Cell lysate was immunoblotted with an anti-integrin α5 and anti- integrin β1 antibody. GAPDH served as an internal control for sample normalization. The integrin α5 expression was significantly higher in trend-like fashion as the pH elevated from 4.4, 5.4, to 7.4 (*indicated p<0.05). (B) CagA phosphorylation of AGS cells co-cultivated with Hp1033 for 8 h at pH 7.4, 5.4 and 4.4, respectively. Cell lysate was immunoblotted with an anti-CagA, Hsp60 and anti-phospho-CagA antibody. The CagA phosphorylation at pH 5.4 was higher than that of pH 4.4 (p<0.05). The data are shown as mean value ± standard deviation of the triplicate experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3757014&req=5

pone-0072735-g001: Integrin α5 expression and CagA phosphorylation after H. pylori infection are pH dependent.(A) Integrin α5 and β1 expressions of AGS cells cultivated alone or co-cultivated with Hp1033 at pH 7.4, 5.4, and 4.4, respectively. Cell lysate was immunoblotted with an anti-integrin α5 and anti- integrin β1 antibody. GAPDH served as an internal control for sample normalization. The integrin α5 expression was significantly higher in trend-like fashion as the pH elevated from 4.4, 5.4, to 7.4 (*indicated p<0.05). (B) CagA phosphorylation of AGS cells co-cultivated with Hp1033 for 8 h at pH 7.4, 5.4 and 4.4, respectively. Cell lysate was immunoblotted with an anti-CagA, Hsp60 and anti-phospho-CagA antibody. The CagA phosphorylation at pH 5.4 was higher than that of pH 4.4 (p<0.05). The data are shown as mean value ± standard deviation of the triplicate experiments.
Mentions: In the absence of H. pylori infection, there were no differences in the integrin α5 and β1 expressions of AGS cells among different pH values at 7.4, 5.4, or 4.4 (Figure 1A). However, the integrin α5 expression, but not integrin β1 expression, was significantly increased in the AGS cells exposed to Hp1033 isolates, when the pH of the culture medium increased from 4.4 to 7.4 (p<0.05, Figure 1A). Moreover, as depicted in Figure 1B, the CagA phosphorylation of AGS cells co-cultivated with Hp1033 was lower at pH 4.4 than at either pH 7.4 or pH 5.4 (p = 0.08 or p<0.01, respectively).

Bottom Line: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk.Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks.In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05).

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

ABSTRACT

Background/aims: H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis.

Methods: The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks.

Results: Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5β1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05).

Conclusions: H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication.

Show MeSH
Related in: MedlinePlus