Clarification of the mechanism of periodontitis-initiated/accelerated atheroacleicsis and identification of its causal components

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Emerging basic scientific studies have supported that infection may represent a risk factor for atherosclerosis. With periodotopathogenic bacteria, Porphyromonas gingivalis, as model pathogen, in vivo studies demonstrated that this organism can accelerate atheroma deposition in animal models. In this study, we first try to determine whether P. gingivalis can up-regulate the expression of the receptors for oxidized LDL in macrophage in vitro. We demonstrated that mouse macrophage cell line, J774.A1 cells were induced to express the receptors (SR-A, CD36 and Lox-1) for oxidized LDL by the stimulation with P. gingivalis, heat-killed bacteria or its fimbriae mutants. Moreover, we found that heat shock protein (HSP) 60 was also induced by the stimulation with P. gingivalis at both mRNA and protein levels. These data support that P. gingivalis stimulate macrophage differentiation to foam cells, a necessary initial event in the development of atherosclerotic plaque lesions.In this study, we i … More nvestigated the mechanisms of pro-inflammatory cytokine inductions in human monocytic cell line (THP-1 cells) by stimulation with recombinant histone-like DNA binding protein (HLP) of Streptococcus intermedius (rSi-HLP): rSi-HLP stimulation-induced production of pro-inflammatory cytokines (IL-8, IL-1β and TNF-α) occurred in a time- and dose-dependent manner. In contrast with the heat-stable activity of DNA binding, the cytokine induction activity of rSi-HLP was heat-unstable. In subsequent studies, rSi-HLP acted cooperatively with lipoteichoic acid, the synthetic Toll-like receptor 2 agonist, Pam3CSK4, and the cytosolic nucleotide binding oligomerization domain 2 receptor agonist, muramyldipeptide. Furthermore, Western blot and blocking assays with specific inhibitors showed that rSi-HLP stimulation induced the activation of cell signal transduction pathways, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK).Collectively, these results demonstrate oral, especially periodotopathic, bacteria can up-regulate inflammatory response and indicate the infection with these bacteria accelerates inflammatory responses, which directly lead to atherosclerosis. Less