Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1

Ann M. O'Hara, Asima Bhattacharyya, Randy C. Mifflin, Michael F. Smith, Kieran A. Ryan, Kevin G E Scott, Makoto Naganuma, Antonella Casola, Tadahide Izumi, Sankar Mitra, Peter B. Ernst, Sheila E. Crowe

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Abstract

Helicobacter pylori infection causes inflammation and increases the expression of IL-8 in human gastric epithelial cells. H. pylori activates NF-κB and AP-1, essential transcriptional factors in H. pylori-induced IL-8 gene transcription. Although colonization creates a local oxidative stress, the molecular basis for the transition from infection to the expression of redox-sensitive cytokine genes is unknown. We recently reported that the expression of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE-1/Ref-1), which repairs oxidative DNA damage and reductively activates transcription factors including AP-1 and NF-κB, is increased in human gastric epithelia during H. pylori infection. In this study, we examine whether APE-1/Ref-1 functions in the modulation of IL-8 gene expression in H. pylori-infected human gastric epithelial cells. Small interfering RNA-mediated silencing of APE-1/ Ref-1 inhibited basal and H. pylori-induced AP-1 and NF-κB DNA-binding activity without affecting the nuclear translocation of these transcription factors and also reduced H. pylori-induced IL-8 mRNA and protein. In contrast, overexpression of APE-1/Ref-1 enhanced basal and H. pylori-induced IL-8 gene transcription, and the relative involvement of AP-1 in inducible IL-8 promoter activity was greater in APE-1/Ref-1 overexpressing cells than in cells with basal levels of APE-l/Ref-1. APE-1/Ref-1 inhibition also reduced other H. pylori-induced chemokine expression. By implicating APE-1/Ref-1 as an important regulator of gastric epithelial responses to H. pylori infection, these data elucidate a novel mechanism controlling transcription and gene expression in bacterial pathogenesis.

Original languageEnglish (US)
Pages (from-to)7990-7999
Number of pages10
JournalJournal of Immunology
Volume177
Issue number11
StatePublished - Dec 1 2006

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DNA-(Apurinic or Apyrimidinic Site) Lyase
Interleukin-8
Helicobacter pylori
Oxidation-Reduction
Stomach
Epithelial Cells
Transcription Factor AP-1
Helicobacter Infections
Genes
Gene Expression
RNA Interference
Chemokines
Small Interfering RNA
DNA Damage
Oxidative Stress
Transcription Factors
Epithelium

ASJC Scopus subject areas

  • Immunology

Cite this

O'Hara, A. M., Bhattacharyya, A., Mifflin, R. C., Smith, M. F., Ryan, K. A., Scott, K. G. E., ... Crowe, S. E. (2006). Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1. Journal of Immunology, 177(11), 7990-7999.

Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1. / O'Hara, Ann M.; Bhattacharyya, Asima; Mifflin, Randy C.; Smith, Michael F.; Ryan, Kieran A.; Scott, Kevin G E; Naganuma, Makoto; Casola, Antonella; Izumi, Tadahide; Mitra, Sankar; Ernst, Peter B.; Crowe, Sheila E.

In: Journal of Immunology, Vol. 177, No. 11, 01.12.2006, p. 7990-7999.

Research output: Contribution to journalArticle

O'Hara, AM, Bhattacharyya, A, Mifflin, RC, Smith, MF, Ryan, KA, Scott, KGE, Naganuma, M, Casola, A, Izumi, T, Mitra, S, Ernst, PB & Crowe, SE 2006, 'Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1', Journal of Immunology, vol. 177, no. 11, pp. 7990-7999.
O'Hara AM, Bhattacharyya A, Mifflin RC, Smith MF, Ryan KA, Scott KGE et al. Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1. Journal of Immunology. 2006 Dec 1;177(11):7990-7999.
O'Hara, Ann M. ; Bhattacharyya, Asima ; Mifflin, Randy C. ; Smith, Michael F. ; Ryan, Kieran A. ; Scott, Kevin G E ; Naganuma, Makoto ; Casola, Antonella ; Izumi, Tadahide ; Mitra, Sankar ; Ernst, Peter B. ; Crowe, Sheila E. / Interleukin-8 induction by Helicobacter pylori in gastric epithelial cells is dependent on apurinic/apyrimidinic endonuclease-1/redox factor-1. In: Journal of Immunology. 2006 ; Vol. 177, No. 11. pp. 7990-7999.
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abstract = "Helicobacter pylori infection causes inflammation and increases the expression of IL-8 in human gastric epithelial cells. H. pylori activates NF-κB and AP-1, essential transcriptional factors in H. pylori-induced IL-8 gene transcription. Although colonization creates a local oxidative stress, the molecular basis for the transition from infection to the expression of redox-sensitive cytokine genes is unknown. We recently reported that the expression of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE-1/Ref-1), which repairs oxidative DNA damage and reductively activates transcription factors including AP-1 and NF-κB, is increased in human gastric epithelia during H. pylori infection. In this study, we examine whether APE-1/Ref-1 functions in the modulation of IL-8 gene expression in H. pylori-infected human gastric epithelial cells. Small interfering RNA-mediated silencing of APE-1/ Ref-1 inhibited basal and H. pylori-induced AP-1 and NF-κB DNA-binding activity without affecting the nuclear translocation of these transcription factors and also reduced H. pylori-induced IL-8 mRNA and protein. In contrast, overexpression of APE-1/Ref-1 enhanced basal and H. pylori-induced IL-8 gene transcription, and the relative involvement of AP-1 in inducible IL-8 promoter activity was greater in APE-1/Ref-1 overexpressing cells than in cells with basal levels of APE-l/Ref-1. APE-1/Ref-1 inhibition also reduced other H. pylori-induced chemokine expression. By implicating APE-1/Ref-1 as an important regulator of gastric epithelial responses to H. pylori infection, these data elucidate a novel mechanism controlling transcription and gene expression in bacterial pathogenesis.",
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AU - Mifflin, Randy C.

AU - Smith, Michael F.

AU - Ryan, Kieran A.

AU - Scott, Kevin G E

AU - Naganuma, Makoto

AU - Casola, Antonella

AU - Izumi, Tadahide

AU - Mitra, Sankar

AU - Ernst, Peter B.

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N2 - Helicobacter pylori infection causes inflammation and increases the expression of IL-8 in human gastric epithelial cells. H. pylori activates NF-κB and AP-1, essential transcriptional factors in H. pylori-induced IL-8 gene transcription. Although colonization creates a local oxidative stress, the molecular basis for the transition from infection to the expression of redox-sensitive cytokine genes is unknown. We recently reported that the expression of apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE-1/Ref-1), which repairs oxidative DNA damage and reductively activates transcription factors including AP-1 and NF-κB, is increased in human gastric epithelia during H. pylori infection. In this study, we examine whether APE-1/Ref-1 functions in the modulation of IL-8 gene expression in H. pylori-infected human gastric epithelial cells. Small interfering RNA-mediated silencing of APE-1/ Ref-1 inhibited basal and H. pylori-induced AP-1 and NF-κB DNA-binding activity without affecting the nuclear translocation of these transcription factors and also reduced H. pylori-induced IL-8 mRNA and protein. In contrast, overexpression of APE-1/Ref-1 enhanced basal and H. pylori-induced IL-8 gene transcription, and the relative involvement of AP-1 in inducible IL-8 promoter activity was greater in APE-1/Ref-1 overexpressing cells than in cells with basal levels of APE-l/Ref-1. APE-1/Ref-1 inhibition also reduced other H. pylori-induced chemokine expression. By implicating APE-1/Ref-1 as an important regulator of gastric epithelial responses to H. pylori infection, these data elucidate a novel mechanism controlling transcription and gene expression in bacterial pathogenesis.

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