Apurinic/apyrimidinic endonuclease 1 regulates inflammatory response in macrophages

Andrej Jedinak, Shailesh Dudhgaonkar, Mark R. Kelley, Daniel Sliva

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The multi-functional apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) DNA repair and redox signaling protein has been shown to have a role in cancer growth and survival, however, little has been investigated concerning its role in inflammation. In this study, an APE1 redox-specific inhibitor (E3330) was used in lypopolysaccharide (LPS)-stimulated macrophages (RAW264.7). E3330 clearly suppressed secretion of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL-6) and IL-12 and inflammatory mediators nitric oxide (NO) as well as prostaglandin E2 (PGE2) from the LPS-stimulated RAW264.7 cells. These data were supported by the down-regulation of the LPS-dependent expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes in the RAW264.7 cells. The effects of E3330 were mediated by the inhibition of transcription factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) in the LPS-stimulated macrophages, both known targets of APE1. In conclusion, pharmacological inhibition of APE1 by E3330 suppresses inflammatory response in activated macrophages and can be considered as a novel therapeutic strategy for the inhibition of tumor-associated macrophages.

Original languageEnglish (US)
Pages (from-to)379-385
Number of pages7
JournalAnticancer Research
Volume31
Issue number2
StatePublished - Feb 1 2011

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Keywords

  • APE1
  • Inflammatory response
  • Macrophages
  • Ref-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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