Effect of NF-κB decoy oligodeoxynucleotide on LPS/high-fat diet-induced atherosclerosis in an animal model

Basic Clin Pharmacol Toxicol. 2010 Dec;107(6):925-30. doi: 10.1111/j.1742-7843.2010.00617.x.

Abstract

Atherosclerosis is a chronic inflammatory process occurring in the walls of arteries, in large part due to the accumulation of inflammatory cells. This study was conducted to determine the effect of nuclear factor (NF)-κB decoy oligodeoxynucleotide (ODN) in an atherosclerosis animal model. The mice received i.p. injections of lipopolysaccharide (LPS, 2 mg/kg) three times a week to induce atherosclerotic change, and fed an atherogenic diet for 12 weeks. NF-κB decoy ODN (0.4 mg/kg) was injected into the tail vein. Treatment with NF-κB decoy ODN decreased pro-inflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-1β and inflammatory markers, vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, in the LPS/Fat-induced mice. In addition, the expression of proteins related to fibrosis, transforming growth factor (TGF)-β1 and fibronectin were markedly decreased in the mice treated with NF-κB decoy ODN compared with the LPS/Fat-induced mice without decoy ODN treatment. These data suggest that NF-κB decoy ODN may exert an inhibitory effect on the expression levels of pro-inflammatory cytokines and cell adhesion molecules in atherosclerotic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / prevention & control*
  • Diet, Atherogenic*
  • Disease Models, Animal
  • Fibronectins / metabolism
  • Inflammation / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / adverse effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Oligodeoxyribonucleotides / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Fibronectins
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • NF-kappaB decoy
  • Oligodeoxyribonucleotides
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1