Abstract
Atherosclerosis, a chronic inflammatory disease of the blood vessels, is one of the most common causes of morbidity and mortality world-wide. Involvement of Porphyromonas gingivalis in atherosclerosis is supported by observations from epidemiological, clinical, immunological, and molecular studies. Previously we reported that P. gingivalis vesicles have a much higher invasive efficiency than their originating cells. Here, we further compare the role of P. gingivalis cells and their vesicles in expression of chemoattractant proteins including CXCL1, CXCL2, and CXCL8, and adhesive molecules such as E-selectin in human umbilical vein endothelial cells (HUVECs). Both P. gingivalis 33277 cells and vesicles were able to up-regulate expression of these molecules, while the vesicles acted as more potent inducers of the inflammatory response associated with the development of atherosclerosis, consequently resulting in significant monocyte adhesion to a monolayer of HUVECs. Interestingly, we found that elevated expression of CXCL8 and E-selectin in endothelial cells induced by P. gingivalis correlated with the invasive ability of P. gingivalis cells and vesicles. Non-invasive bacterial cells and vesicles had no effect on expression of these genes. This study highlights the potential risk of P. gingivalis cells and vesicles in initiation of atherosclerosis and provides a potential target for the development of novel therapeutics against bacteria-associated atherosclerosis.
Highlights
Porphyromonas gingivalis, a Gram-negative bacterium, is associated with chronic periodontitis and with several systemic diseases including atherosclerosis (Lamont and Jenkinson, 1998; XiménezFyvie et al, 2000; Hajishengallis et al, 2012; Hussain et al, 2015)
Innate immune responses in human umbilical vein endothelial cells (HUVECs) induced by P. gingivalis cells or vesicles were first examined using a PCR array that includes 84 key genes involved in innate immune response
There was no significant alteration in expression of these inflammatory genes in the HUVECs treated with P. gingivalis cells or vesicles, except for the vesicles derived from the fimA mutant (FAE)
Summary
Porphyromonas gingivalis, a Gram-negative bacterium, is associated with chronic periodontitis and with several systemic diseases including atherosclerosis (Lamont and Jenkinson, 1998; XiménezFyvie et al, 2000; Hajishengallis et al, 2012; Hussain et al, 2015). Previous studies demonstrated that P. gingivalis disrupts tissue homeostasis through manipulation of innate immunity, including complement and proinflammatory cytokines (Hajishengallis and Lamont, 2014; Hajishengallis, 2015). We recently demonstrated that P. gingivalis vesicles exhibit much higher invasive efficiency than their originating bacterial cells, it appears that both invasive processes involve a clathrin-mediated endocytic machinery (Ho et al, 2015, 2016). P. gingivalis vesicles appeared to repress immune responses induced by IFN-γ. Expression of several genes involved in IFN-γ signal transduction, including genes encoding class II transactivator, Jak, and Jak, proteins required for expression of MHC class II molecules, were down-regulated in vascular endothelial cells in the presence of P. gingivalis vesicles (Srisatjaluk et al, 2002). Since MHC class II molecules are essential for antigen presentation, it is likely that inhibition of their expression facilitates P. gingivalis’ escape from immune surveillance
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