Porphyromonas gingivalis antigens and interleukin-6 stimulate the production of monocyte chemoattractant protein-1 via the upregulation of early growth response-1 transcription in human coronary artery endothelial cells

J Vasc Res. 2010;47(4):346-54. doi: 10.1159/000265568. Epub 2009 Dec 16.

Abstract

Background: Individuals with periodontitis have elevated serum levels of IL-6 and C-reactive protein and have been reported to have a significantly increased risk of developing cardiovascular disease. The transcription factor early growth response factor 1 (Egr-1) has been shown to play an important role in the development and progression of atherosclerosis. However, it is not known whether periodontal infection affects the expression of Egr-1 and subsequent endothelial cells expression of monocyte chemoattractant protein (MCP)-1, a key molecule of leukocyte chemoattraction into vessels.

Methods: Human coronary artery endothelial cells (HCAECs) were stimulated with either sonicated extracts from Porphyromonas gingivalis strains 381 or SU63, or a combination of IL-6 and soluble IL-6 receptor (IL-6/sIL-6R). The expression of Egr-1, and subsequently MCP-1, was then analyzed. The role of Egr-1 on MCP-1 expression was analyzed by siRNA transfection.

Results: Both P. gingivalis antigens and IL-6/sIL-6R stimulations upregulated the expression of Egr-1, with a more robust effect by IL-6/sIL-6R. Increased expression of Egr-1 coincided with MCP-1 production, and Egr-1 downregulation by siRNA suppressed this effect.

Conclusion: These results clearly suggest that periodontal infection has the potential to affect HCAECs and hence contribute to the development of subsequent atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / immunology*
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Coronary Vessels / immunology*
  • Coronary Vessels / metabolism
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Endothelial Cells / immunology*
  • Endothelial Cells / metabolism
  • Humans
  • Interleukin-6 / metabolism*
  • Porphyromonas gingivalis / immunology*
  • RNA Interference
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-6 / metabolism
  • Recombinant Proteins / metabolism
  • Up-Regulation

Substances

  • Antigens, Bacterial
  • CCL2 protein, human
  • Chemokine CCL2
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • IL6 protein, human
  • IL6R protein, human
  • Interleukin-6
  • RNA, Messenger
  • Receptors, Interleukin-6
  • Recombinant Proteins