HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages.

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 E(2) (PGE(2)) 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.
AuthorsAndrej Jedinak, Shailesh Dudhgaonkar, Mark R Kelley, Daniel Sliva
JournalAnticancer research (Anticancer Res) Vol. 31 Issue 2 Pg. 379-85 (Feb 2011) ISSN: 1791-7530 [Electronic] Greece
PMID21378315 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzoquinones
  • Lipopolysaccharides
  • NF-kappa B
  • Propionates
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • E 3330
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Apex1 protein, mouse
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Dinoprostone
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzoquinones (pharmacology)
  • Cells, Cultured
  • Cyclooxygenase 2 (biosynthesis)
  • DNA-(Apurinic or Apyrimidinic Site) Lyase (antagonists & inhibitors, immunology, metabolism)
  • Dinoprostone (immunology, metabolism)
  • Lipopolysaccharides (pharmacology)
  • Macrophages (drug effects, enzymology, immunology)
  • Mice
  • NF-kappa B (immunology, metabolism)
  • Nitric Oxide (immunology, metabolism)
  • Nitric Oxide Synthase Type II (biosynthesis)
  • Oxidation-Reduction
  • Propionates (pharmacology)
  • Signal Transduction
  • Transcription Factor AP-1 (immunology, metabolism)
  • Tumor Necrosis Factor-alpha (biosynthesis)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: