Exp Mol Med.  2011 Sep;43(9):510-516. 10.3858/emm.2011.43.9.058.

Down-regulation of ATP-binding cassette transporter G1 expression by unmethylated CpG oligodeoxynucleotides in RAW 264.7 macrophages

Affiliations
  • 1National Research Laboratory of Molecular Virology, Department of Pathology, The Catholic University of Korea, School of Medicine, Seoul 137-701, Korea. jiyou@catholic.ac.kr
  • 2Department of Nutritional Sciences, University of Connecticut, Storrs CT 06269, USA.
  • 3Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Korea.

Abstract

We have investigated the effect of various forms of phosphodiester cytidine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) on the production of pro-inflammatory cytokines and related genes in RAW 264.7 macrophages. Treatment with the CpG ODNs increased the expression of tumor necrosis factor alpha (TNF-alpha), IL-6, and inducible nitric oxide synthase but not interleukin-1beta (IL-1beta). We also investigated the effect of CpG ODNs on the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) genes which are known to facilitate cholesterol efflux from macrophages for anti-atherosclerosis. CpG 2006 significantly reduced the levels of ABCG1 mRNA as determined by real-time polymerase chain reaction, whereas ABCA1 mRNA level was not changed. Western blot analysis further confirmed the reduction of ABCG1 protein expression by CpG 2006. In addition, we also determined the protein level of peroxisome proliferator activated receptor gamma (PPARgamma), which is recognized as a transcriptional activator of ABC transporters, was also reduced by CpG 2006. Thus, these results suggest that ABCG1 is specifically down-regulated by CpG 2006 in a PPARgamma-dependent manner in macrophages.

Keyword

atherosclerosis; ATP-binding cassette transpoters; cholesterol; CpG oligonucleotide; macrophages

MeSH Terms

ATP-Binding Cassette Transporters/drug effects/genetics/*metabolism
Animals
Atherosclerosis/metabolism
Cholesterol/metabolism
Cytokines/drug effects/metabolism
Gene Expression Regulation
Inflammation/*metabolism
Interleukin-1beta/drug effects/metabolism
Interleukin-6/metabolism
Lipoproteins/drug effects/genetics/*metabolism
Macrophages/*cytology/*metabolism
Mice
Nitric Oxide Synthase/drug effects/metabolism
Oligodeoxyribonucleotides/*pharmacology
PPAR gamma/genetics/*metabolism
Tumor Necrosis Factor-alpha/drug effects/metabolism
Full Text Links
  • EMM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr