E-selectin expression induced by Porphyromonas gingivalis in human endothelial cells via nucleotide-binding oligomerization domain-like receptors and Toll-like receptors.

Porphyromonas gingivalis, an important periodontal pathogen, has been proved to actively invade cells, induce endothelial cell activation, and promote development of atherosclerosis. Innate immune surveillance, which includes the activity of nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and Toll-like receptors (TLRs), are essential for the control of microbial infections; however, the roles of receptor families in P. gingivalis infections remain unclear. Here, we examined the roles of NLRs and TLRs in endothelial cell activation caused by P. gingivalis. Live P. gingivalis and whole cell sonicates were used to stimulate endothelial cells, and both showed upregulation of E-selectin as well as NOD1, NOD2, and TLR2. In addition, silencing of these genes in endothelial cells infected with P. gingivalis led to a reduction in E-selectin expression. Porphyromonas gingivalis also induced nuclear factor-κB (NF-κB) and P38 mitogen-activated protein kinase (MAPK) activity in endothelial cells, whereas small interfering RNA targeting NOD1 significantly reduced these signals. Moreover, inhibition of either NOD2 or TLR2 inhibited NF-κB significantly, but had only a weak inhibitory effect on P38 MAPK signaling. Direct inhibition of NF-κB and P38 MAPK significantly attenuated E-selectin expression induced by P. gingivalis in endothelial cells. Taken together, these findings suggest that NOD1, NOD2, and TLR2 play important, non-redundant roles in endothelial cell activation following P. gingivalis infection.