PT  - JOURNAL ARTICLE
AU  - JEDINAK, ANDREJ
AU  - DUDHGAONKAR, SHAILESH
AU  - KELLEY, MARK R.
AU  - SLIVA, DANIEL
TI  - Apurinic/Apyrimidinic Endonuclease 1 Regulates Inflammatory Response in Macrophages
DP  - 2011 Feb 01
TA  - Anticancer Research
PG  - 379--385
VI  - 31
IP  - 2
4099  - http://ar.iiarjournals.org/content/31/2/379.short
4100  - http://ar.iiarjournals.org/content/31/2/379.full
SO  - Anticancer Res2011 Feb 01; 31
AB  - 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.