Streptococcus oralis coaggregation receptor polysaccharides induce inflammatory responses in human aortic endothelial cells

Abstract

Streptococcus oralis, belonging to the oral viridans group streptococci, has been detected in human cardiovascular lesions including infective endocarditis and atheromatous plaques. The organism has coaggregation receptor polysaccharides (RPS) on the cell wall, which function as receptors for surface adhesins on other members of the oral biofilm community. The present study examined the capacity of S. oralis RPS to induce inflammatory responses in human aortic endothelial cells (HAECs). Purified RPS was used to stimulate HAECs, and the induction of cytokines, adhesion molecules and Toll-like receptors (TLRs) was examined. Involvement of RPS in HAEC invasion by S. oralis was also examined. RPS-stimulated HAECs produced more cytokines (interleukin-6, interleukin-8 and monocyte chemoattractant protein-1) and intercellular adhesion molecule-1 than non-stimulated HAECs. The messenger RNA (mRNA) expression of cytokines and adhesion molecules in RPS-stimulated HAECs increased markedly compared with that in non-stimulated HAECs. Upregulation of TLR-2 mRNA expression was demonstrated in RPS-stimulated HAECs. Moreover, TLR-2 mRNA expression and cytokine production were reduced by the incubation of HAECs with inhibitors against p38 mitogen-activated protein kinase and nuclear factor-κB. An RPS-defective mutant of S. oralis showed greater invasion into HAECs than an RPS-possessing strain. However, HAECs invaded by the RPS-defective mutant produced less cytokines than HAECs invaded by the RPS-possessing strain, indicating that RPS can stimulate HAECs intracellularly. These results suggest that S. oralis RPS may be an important contributor to the pathogenesis of cardiovascular diseases such as infective endocarditis and atherosclerosis.