Apurinic/apyrimidinic endonuclease 1 regulates inflammatory response in macrophages

Andrej Jedinak, Shailesh Dudhgaonkar, Mark Kelley, Daniel Sliva

Research output: Contribution to journalArticle

23 Citations (Scopus)

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

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DNA-(Apurinic or Apyrimidinic Site) Lyase
Macrophages
Oxidation-Reduction
Interleukin-6
Endonucleases
Transcription Factor AP-1
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Interleukin-12
Dinoprostone
DNA Repair
Neoplasms
Nitric Oxide
Transcription Factors
Down-Regulation
Tumor Necrosis Factor-alpha
Pharmacology
Cytokines
Inflammation
E 3330

Keywords

  • APE1
  • Inflammatory response
  • Macrophages
  • Ref-1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Apurinic/apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. / Jedinak, Andrej; Dudhgaonkar, Shailesh; Kelley, Mark; Sliva, Daniel.

In: Anticancer Research, Vol. 31, No. 2, 02.2011, p. 379-385.

Research output: Contribution to journalArticle

Jedinak, A, Dudhgaonkar, S, Kelley, M & Sliva, D 2011, 'Apurinic/apyrimidinic endonuclease 1 regulates inflammatory response in macrophages', Anticancer Research, vol. 31, no. 2, pp. 379-385.
Jedinak, Andrej ; Dudhgaonkar, Shailesh ; Kelley, Mark ; Sliva, Daniel. / Apurinic/apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. In: Anticancer Research. 2011 ; Vol. 31, No. 2. pp. 379-385.
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