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.


CONCLUSIONS
These results clearly suggest that periodontal infection has the potential to affect HCAECs and hence contribute to the development of subsequent atherosclerosis.
Maekawa
Tomoki
T
Center for Transdisciplinary Research, Niigata University, Niigata 951-8514, Japan.
Takahashi
Naoki
N
Honda
Tomoyuki
T
Yonezawa
Daisuke
D
Miyashita
Hirotaka
H
Okui
Takafumi
T
Tabeta
Koichi
K
Yamazaki
Kazuhisa
K
D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000276:immunology* / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
D000942:Antigens, Bacterial; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins