Intracellular Osteopontin Induced by CagA-positive Helicobacter pylori Promotes Beta-catenin Accumulation and Interleukin-8 Secretion in Gastric Epithelial cells

Wei Lun Chang, Hsiao Bai Yang, Hsiu Chi Cheng, Yi Chun Yeh, Cheng Yen Kao, Jiunn Jong Wu, Cheng Chan Lu, Bor Shyang Sheu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Osteopontin, an important immune modulator and oncogenic promoter, is upregulated in H. pylori-infected gastric mucosa. However, the underlying mechanisms and biological significance are poorly understood. We investigated whether osteopontin was upregulated in gastric epithelial cells by H. pylori and the virulence factors involved. Moreover, cellular component changes caused by osteopontin were also investigated. Materials and Methods: The gastric epithelial cell line MKN45 was cocultured with wild-type and mutant H. pylori to analyze osteopontin expression. Beta-catenin levels in cell lysate and interleukin-8 levels in supernatant were analyzed. The difference in osteopontin expression levels in both gastric epithelium and plasma was compared between H. pylori-infected patients and uninfected controls. Results: H. pylori induced intracellular, but not secretory, osteopontin expression in MKN45 cells. Accordingly, osteopontin expression intensity in gastric epithelium was higher in H. pylori-infected patients than in controls, but osteopontin levels in plasma were similar between both patient groups. H. pylori virulence factor CagA delivered via the type IV secretion system was essential for intracellular osteopontin upregulation. H. pylori induced β-catenin accumulation and interleukin-8 secretion, whereas osteopontin knockdown completely abrogated these effects, in MKN45 cells. TLR2 antagonist abolished iOPN expression induced by H. pylori gastritis strain, but not by H. pylori cancer strain. Conclusions: H. pylori is dependent on CagA translocation via the type IV secretion system to induce intracellular osteopontin expression in gastric epithelial cells. Upregulated intracellular osteopontin may promote gastric carcinogenesis via increased β-catenin accumulation and interleukin-8 secretion.

Original languageEnglish
Pages (from-to)476-484
Number of pages9
JournalHelicobacter
Volume20
Issue number6
DOIs
Publication statusPublished - 2015 Dec 1

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Osteopontin
beta Catenin
Pylorus
Interleukin-8
Helicobacter pylori
Stomach
Epithelial Cells
Catenins
Virulence Factors
Epithelium
Gastritis
Gastric Mucosa
Carcinogenesis
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Gastroenterology
  • Infectious Diseases

Cite this

@article{6d2e43ae35274157ae7b85d39d9ab8e7,
title = "Intracellular Osteopontin Induced by CagA-positive Helicobacter pylori Promotes Beta-catenin Accumulation and Interleukin-8 Secretion in Gastric Epithelial cells",
abstract = "Background: Osteopontin, an important immune modulator and oncogenic promoter, is upregulated in H. pylori-infected gastric mucosa. However, the underlying mechanisms and biological significance are poorly understood. We investigated whether osteopontin was upregulated in gastric epithelial cells by H. pylori and the virulence factors involved. Moreover, cellular component changes caused by osteopontin were also investigated. Materials and Methods: The gastric epithelial cell line MKN45 was cocultured with wild-type and mutant H. pylori to analyze osteopontin expression. Beta-catenin levels in cell lysate and interleukin-8 levels in supernatant were analyzed. The difference in osteopontin expression levels in both gastric epithelium and plasma was compared between H. pylori-infected patients and uninfected controls. Results: H. pylori induced intracellular, but not secretory, osteopontin expression in MKN45 cells. Accordingly, osteopontin expression intensity in gastric epithelium was higher in H. pylori-infected patients than in controls, but osteopontin levels in plasma were similar between both patient groups. H. pylori virulence factor CagA delivered via the type IV secretion system was essential for intracellular osteopontin upregulation. H. pylori induced β-catenin accumulation and interleukin-8 secretion, whereas osteopontin knockdown completely abrogated these effects, in MKN45 cells. TLR2 antagonist abolished iOPN expression induced by H. pylori gastritis strain, but not by H. pylori cancer strain. Conclusions: H. pylori is dependent on CagA translocation via the type IV secretion system to induce intracellular osteopontin expression in gastric epithelial cells. Upregulated intracellular osteopontin may promote gastric carcinogenesis via increased β-catenin accumulation and interleukin-8 secretion.",
author = "Chang, {Wei Lun} and Yang, {Hsiao Bai} and Cheng, {Hsiu Chi} and Yeh, {Yi Chun} and Kao, {Cheng Yen} and Wu, {Jiunn Jong} and Lu, {Cheng Chan} and Sheu, {Bor Shyang}",
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pages = "476--484",
journal = "Helicobacter",
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Intracellular Osteopontin Induced by CagA-positive Helicobacter pylori Promotes Beta-catenin Accumulation and Interleukin-8 Secretion in Gastric Epithelial cells. / Chang, Wei Lun; Yang, Hsiao Bai; Cheng, Hsiu Chi; Yeh, Yi Chun; Kao, Cheng Yen; Wu, Jiunn Jong; Lu, Cheng Chan; Sheu, Bor Shyang.

In: Helicobacter, Vol. 20, No. 6, 01.12.2015, p. 476-484.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intracellular Osteopontin Induced by CagA-positive Helicobacter pylori Promotes Beta-catenin Accumulation and Interleukin-8 Secretion in Gastric Epithelial cells

AU - Chang, Wei Lun

AU - Yang, Hsiao Bai

AU - Cheng, Hsiu Chi

AU - Yeh, Yi Chun

AU - Kao, Cheng Yen

AU - Wu, Jiunn Jong

AU - Lu, Cheng Chan

AU - Sheu, Bor Shyang

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: Osteopontin, an important immune modulator and oncogenic promoter, is upregulated in H. pylori-infected gastric mucosa. However, the underlying mechanisms and biological significance are poorly understood. We investigated whether osteopontin was upregulated in gastric epithelial cells by H. pylori and the virulence factors involved. Moreover, cellular component changes caused by osteopontin were also investigated. Materials and Methods: The gastric epithelial cell line MKN45 was cocultured with wild-type and mutant H. pylori to analyze osteopontin expression. Beta-catenin levels in cell lysate and interleukin-8 levels in supernatant were analyzed. The difference in osteopontin expression levels in both gastric epithelium and plasma was compared between H. pylori-infected patients and uninfected controls. Results: H. pylori induced intracellular, but not secretory, osteopontin expression in MKN45 cells. Accordingly, osteopontin expression intensity in gastric epithelium was higher in H. pylori-infected patients than in controls, but osteopontin levels in plasma were similar between both patient groups. H. pylori virulence factor CagA delivered via the type IV secretion system was essential for intracellular osteopontin upregulation. H. pylori induced β-catenin accumulation and interleukin-8 secretion, whereas osteopontin knockdown completely abrogated these effects, in MKN45 cells. TLR2 antagonist abolished iOPN expression induced by H. pylori gastritis strain, but not by H. pylori cancer strain. Conclusions: H. pylori is dependent on CagA translocation via the type IV secretion system to induce intracellular osteopontin expression in gastric epithelial cells. Upregulated intracellular osteopontin may promote gastric carcinogenesis via increased β-catenin accumulation and interleukin-8 secretion.

AB - Background: Osteopontin, an important immune modulator and oncogenic promoter, is upregulated in H. pylori-infected gastric mucosa. However, the underlying mechanisms and biological significance are poorly understood. We investigated whether osteopontin was upregulated in gastric epithelial cells by H. pylori and the virulence factors involved. Moreover, cellular component changes caused by osteopontin were also investigated. Materials and Methods: The gastric epithelial cell line MKN45 was cocultured with wild-type and mutant H. pylori to analyze osteopontin expression. Beta-catenin levels in cell lysate and interleukin-8 levels in supernatant were analyzed. The difference in osteopontin expression levels in both gastric epithelium and plasma was compared between H. pylori-infected patients and uninfected controls. Results: H. pylori induced intracellular, but not secretory, osteopontin expression in MKN45 cells. Accordingly, osteopontin expression intensity in gastric epithelium was higher in H. pylori-infected patients than in controls, but osteopontin levels in plasma were similar between both patient groups. H. pylori virulence factor CagA delivered via the type IV secretion system was essential for intracellular osteopontin upregulation. H. pylori induced β-catenin accumulation and interleukin-8 secretion, whereas osteopontin knockdown completely abrogated these effects, in MKN45 cells. TLR2 antagonist abolished iOPN expression induced by H. pylori gastritis strain, but not by H. pylori cancer strain. Conclusions: H. pylori is dependent on CagA translocation via the type IV secretion system to induce intracellular osteopontin expression in gastric epithelial cells. Upregulated intracellular osteopontin may promote gastric carcinogenesis via increased β-catenin accumulation and interleukin-8 secretion.

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U2 - 10.1111/hel.12225

DO - 10.1111/hel.12225

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