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

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.