Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1, and NF-κB and induces chemokine expression in gastric epithelial AGS cells

Ji Hye Seo, Joo Weon Lim, Hye Young Kim, Kyung Hwan Kim

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Oxidant-sensitive transcription factors, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) have been considered as the regulators of inducible genes such as chemokines. Since oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis, chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) may be regulated by NF-κB and/or AP-1. Ras, the upstream activator for mitogen-activated protein kinase (MAPK) and MAPK cascade regulate AP-1 activation. The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of chemokines (IL-8, MCP-1), which is regulated by Ras, MAPK, AP-1, and NF-κB in gastric epithelial AGS cells, and whether these transcriptional regulations of chemokines are inhibited by transfection with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IκBα (MAD-3) or treatment with MAPK inhibitors (U0126 for extracellular signal-regulated kinase or SB203580 for p38 kinase). In addition, virulence factors of HP99 were characterized by PCR analysis for the isolated DNA. As a result, HP99 is identified as cagA +, vacA s1b, m2, iceA1 H. pylori strain. HP99 induced a time-dependent expression of mRNA and protein for IL-8 and MCP-1 via mediation of MAPK, AP-1, and NF-κB. Transfection with mutant genes for Ras, c-Jun, and IκBα and treatment with MAPK inhibitors suppressed H. pylori-induced activation of transcription factors (NF-κB, AP-1) and expression of chemokines (IL-8, MCP-1) in AGS cells. In conclusion, Ras and MAPK cascade may act as the upstream signaling for the activation of AP-1 and NF-κB, which induce chemokine expression in H. pylori-infected AGS cells. Specific targeting of the activation of NF-κB and AP-1 may be effective for the prevention or treatment of gastric inflammation associated with H. pylori infection.

Original languageEnglish
Pages (from-to)49-62
Number of pages14
JournalLaboratory Investigation
Volume84
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1

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Transcription Factor AP-1
Mitogen-Activated Protein Kinases
Chemokines
Helicobacter pylori
Stomach
Epithelial Cells
Chemokine CCL2
Interleukin-8
Protein Kinase Inhibitors
Transfection
Transcription Factors
jun Genes
ras Genes
Extracellular Signal-Regulated MAP Kinases
Helicobacter Infections
Virulence Factors
Regulator Genes
Oxidants
Reactive Oxygen Species
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1, and NF-κB and induces chemokine expression in gastric epithelial AGS cells",
abstract = "Oxidant-sensitive transcription factors, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) have been considered as the regulators of inducible genes such as chemokines. Since oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis, chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) may be regulated by NF-κB and/or AP-1. Ras, the upstream activator for mitogen-activated protein kinase (MAPK) and MAPK cascade regulate AP-1 activation. The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of chemokines (IL-8, MCP-1), which is regulated by Ras, MAPK, AP-1, and NF-κB in gastric epithelial AGS cells, and whether these transcriptional regulations of chemokines are inhibited by transfection with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IκBα (MAD-3) or treatment with MAPK inhibitors (U0126 for extracellular signal-regulated kinase or SB203580 for p38 kinase). In addition, virulence factors of HP99 were characterized by PCR analysis for the isolated DNA. As a result, HP99 is identified as cagA +, vacA s1b, m2, iceA1 H. pylori strain. HP99 induced a time-dependent expression of mRNA and protein for IL-8 and MCP-1 via mediation of MAPK, AP-1, and NF-κB. Transfection with mutant genes for Ras, c-Jun, and IκBα and treatment with MAPK inhibitors suppressed H. pylori-induced activation of transcription factors (NF-κB, AP-1) and expression of chemokines (IL-8, MCP-1) in AGS cells. In conclusion, Ras and MAPK cascade may act as the upstream signaling for the activation of AP-1 and NF-κB, which induce chemokine expression in H. pylori-infected AGS cells. Specific targeting of the activation of NF-κB and AP-1 may be effective for the prevention or treatment of gastric inflammation associated with H. pylori infection.",
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Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1, and NF-κB and induces chemokine expression in gastric epithelial AGS cells. / Seo, Ji Hye; Lim, Joo Weon; Kim, Hye Young; Kim, Kyung Hwan.

In: Laboratory Investigation, Vol. 84, No. 1, 01.01.2004, p. 49-62.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1, and NF-κB and induces chemokine expression in gastric epithelial AGS cells

AU - Seo, Ji Hye

AU - Lim, Joo Weon

AU - Kim, Hye Young

AU - Kim, Kyung Hwan

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N2 - Oxidant-sensitive transcription factors, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) have been considered as the regulators of inducible genes such as chemokines. Since oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis, chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) may be regulated by NF-κB and/or AP-1. Ras, the upstream activator for mitogen-activated protein kinase (MAPK) and MAPK cascade regulate AP-1 activation. The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of chemokines (IL-8, MCP-1), which is regulated by Ras, MAPK, AP-1, and NF-κB in gastric epithelial AGS cells, and whether these transcriptional regulations of chemokines are inhibited by transfection with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IκBα (MAD-3) or treatment with MAPK inhibitors (U0126 for extracellular signal-regulated kinase or SB203580 for p38 kinase). In addition, virulence factors of HP99 were characterized by PCR analysis for the isolated DNA. As a result, HP99 is identified as cagA +, vacA s1b, m2, iceA1 H. pylori strain. HP99 induced a time-dependent expression of mRNA and protein for IL-8 and MCP-1 via mediation of MAPK, AP-1, and NF-κB. Transfection with mutant genes for Ras, c-Jun, and IκBα and treatment with MAPK inhibitors suppressed H. pylori-induced activation of transcription factors (NF-κB, AP-1) and expression of chemokines (IL-8, MCP-1) in AGS cells. In conclusion, Ras and MAPK cascade may act as the upstream signaling for the activation of AP-1 and NF-κB, which induce chemokine expression in H. pylori-infected AGS cells. Specific targeting of the activation of NF-κB and AP-1 may be effective for the prevention or treatment of gastric inflammation associated with H. pylori infection.

AB - Oxidant-sensitive transcription factors, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) have been considered as the regulators of inducible genes such as chemokines. Since oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis, chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) may be regulated by NF-κB and/or AP-1. Ras, the upstream activator for mitogen-activated protein kinase (MAPK) and MAPK cascade regulate AP-1 activation. The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of chemokines (IL-8, MCP-1), which is regulated by Ras, MAPK, AP-1, and NF-κB in gastric epithelial AGS cells, and whether these transcriptional regulations of chemokines are inhibited by transfection with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IκBα (MAD-3) or treatment with MAPK inhibitors (U0126 for extracellular signal-regulated kinase or SB203580 for p38 kinase). In addition, virulence factors of HP99 were characterized by PCR analysis for the isolated DNA. As a result, HP99 is identified as cagA +, vacA s1b, m2, iceA1 H. pylori strain. HP99 induced a time-dependent expression of mRNA and protein for IL-8 and MCP-1 via mediation of MAPK, AP-1, and NF-κB. Transfection with mutant genes for Ras, c-Jun, and IκBα and treatment with MAPK inhibitors suppressed H. pylori-induced activation of transcription factors (NF-κB, AP-1) and expression of chemokines (IL-8, MCP-1) in AGS cells. In conclusion, Ras and MAPK cascade may act as the upstream signaling for the activation of AP-1 and NF-κB, which induce chemokine expression in H. pylori-infected AGS cells. Specific targeting of the activation of NF-κB and AP-1 may be effective for the prevention or treatment of gastric inflammation associated with H. pylori infection.

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