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

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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