P. gingivalis is a major pathogen that is involved in the onset and progression of periodontal disease. This study investigated the effect of resveratrol, a naturally occurring polyphenol, on P. gingivalis LPS-accelerated vascular inflammation, a key step in the progression of periodontitis. Resveratrol significantly inhibited the P. gingivalis LPS-induced adhesion of leukocytes to endothelial cells and to the aortic endothelium by down-regulating the cell adhesion molecules, ICAM-1 and VCAM-1. Moreover, the inhibition of the P. gingivalis LPS-induced cell adhesion molecules by resveratrol was mainly mediated by nuclear factor-kappaB (NF-kappaB). Resveratrol suppressed P. gingivalis LPS-stimulated IkappaBalpha phosphorylation and nuclear translocation of the p65 subunit of NF-kappaB in HMECs. Overall, these findings suggest that resveratrol significantly attenuates the P. gingivalis LPS-induced monocyte adhesion to the endothelium by suppressing the expression of the NF-kappaB-dependent cell adhesion molecules, suggesting its therapeutic role in periodontal pathogen-induced vascular inflammation.
Porphyromonas gingivalis is a major periodontal pathogen. The lipopolysaccharide (LPS) secreted from P. gingivalis is implicated in the initiation and progression of periodontitis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. In this study, we report that P. gingivalis LPS activates angiogenic cascade, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). Furthermore, P. gingivalis LPS potently stimulated in vivo neovascularization in chick chorioallantoic membrane (CAM) and the mouse Matrigel plug assay. P. gingivalis LPS had no effect on the expression of vascular endothelial growth factor (VEGF) or its receptor, Flk-1, implying that P. gingivalis LPS-induced angiogenesis may result from its direct action on endothelial cells. P. gingivalis LPS evoked activation of the mitogen-activated protein kinase ERK1/2 in HUVECs, which is closely linked to angiogenesis. Taken together, these results strongly suggest P. gingivalis LPS plays an important role in the pathological angiogenesis for periodontal diseases, such as periodontitis.
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