Porphyromonas gingivalis regulates atherosclerosis through an immune pathway.

Atherosclerosis (AS) is a chronic inflammatory disease, involving a pathological process of endothelial dysfunction, lipid deposition, plaque rupture, and arterial occlusion, and is one of the leading causes of death in the world population. The progression of AS is closely associated with several inflammatory diseases, among which periodontitis has been shown to increase the risk of AS. Porphyromonas gingivalis (P. gingivalis), presenting in large numbers in subgingival plaque biofilms, is the "dominant flora" in periodontitis, and its multiple virulence factors are important in stimulating host immunity. Therefore, it is significant to elucidate the potential mechanism and association between P. gingivalis and AS to prevent and treat AS. By summarizing the existing studies, we found that P. gingivalis promotes the progression of AS through multiple immune pathways. P. gingivalis can escape host immune clearance and, in various forms, circulate with blood and lymph and colonize arterial vessel walls, directly inducing local inflammation in blood vessels. It also induces the production of systemic inflammatory mediators and autoimmune antibodies, disrupts the serum lipid profile, and thus promotes the progression of AS. In this paper, we summarize the recent evidence (including clinical studies and animal studies) on the correlation between P. gingivalis and AS, and describe the specific immune mechanisms by which P. gingivalis promotes AS progression from three aspects (immune escape, blood circulation, and lymphatic circulation), providing new insights into the prevention and treatment of AS by suppressing periodontal pathogenic bacteria.

TLR-4 targeting contributes to the recovery of osteoimmunology in periodontitis.

OBJECTIVE: The aim of this study was to determine the potential role of TLR-4 in the osteoimmunological imbalance of periodontitis. BACKGROUND: Although current evidence supports that TLR-4 plays an important role in the inflammatory response of periodontal tissues triggered by microorganisms, little information is available regarding the function of TLR-4 in the osteoimmune regulation of homeostasis in periodontitis. METHODS: Human gingival epithelial cells (HGEC) were isolated from the gingival tissues of 3 healthy volunteers and the expression of osteoclastogenic cytokines was evaluated by ELISA and real time RT-PCR. In addition, 30 C57BL/6 mice were used and randomly divided into three groups: control group, periodontitis group (CP) and periodontitis+TAK-242 (a specific inhibitor of TLR-4) group (TAK-242) and the expression of osteoclastogenic cytokines and the osteoclast density in the periodontal tissue were evaluated by immunohistochemical staining and tartrate resistant acid phosphatase staining. Moreover, micro-computed tomography (Micro-CT) was used to assess bone resorption. RESULTS: The in vitro results showed that TAK-242 blocked the overproduction of IL-1, IL-6, TNF-α and RANKL in HGEC treated with LPS. The in vivo results revealed that TAK-242 also effectively decreased these osteoclastogenic cytokines in periodontal tissue of mice with periodontitis. More importantly, Micro-CT analysis showed a significant reduction of the alveolar bone loss in the TAK-242 group compared with the CP group. Furthermore, the TRAP staining showed a significant lower density of osteoclasts in the alveolar bone area of the TAK-242 group. CONCLUSION: TLR-4 inhibition decreased the differentiation of osteoclast through the inhibition of the overproduction of osteoclastogenic cytokines and the prevention of the alveolar bone absorption in mouse periodontitis models. Therefore, the use of TAK-242 might contribute to the recovery of the osteoimmunological homeostasis and might provide a potential strategy to treat periodontal diseases.

TLR4 gene in the regulation of periodontitis and its molecular mechanism.

Regulatory effect of Toll-like receptor 4 (TLR4) gene on periodontitis in mice was investigated to explore its possible mechanism. Thirty C57/BL6 mice were randomly divided into the blank control group (N group, n=10), the periodontitis group (P group, n=10) and the periodontitis + TAK-242 group (PT group, n=10). The mice in P and PT group were ligatured with silk threads dipped with porphyromonas gingivalis (P. gingivalis) in the logarithmic phase to induce experimental periodontitis, and TAK-242 was intraperitoneally injected on the day when the periodontitis model was established. After fasting for 8 h, the expression levels of high-sensitivity C-reactive protein and inflammatory cytokines were measured in each group of mice. Their alveolar bones were isolated and changes were detected. Quantitative polymerase chain reaction was used to detect the expression levels of TLR4. After the mice were given TAK-242, the levels of hs-CPR, MCP-1, IL-6 and IL-1ß in the PT group evidently increased (P<0.01) compared with those in the N group. After the mice were administered TAK-242, the alveolar bone density, the percentage of bone volume and the number of bone trabeculae in PT group were significantly reduced, and the bone trabecular space and structural model index were evidently decreased (P<0.01). In addition, the expression levels of and T-bet/GATA3 messenger ribonucleic acids (mRNAs) in peria of mice in the P group were significantly higher than those in the N group (P<0.01), whereas the expression level of Foxp3 mRNA was notably decreased (P<0.01). The involvement of TLR4 gene in the inflammatory response of periodontitis results in periodontitis, and its mechanism may be that it activates TLR4, so as to affect the expression of T-bet, GATA3 and Foxp3.