Sitagliptin Attenuates Porphyromonas Gingivalis Virulence and Inflammatory Response in Macrophage on Titanium

BackgroundIn peri-implantitis, porphyromonas gingivalis and macrophage play central roles. The aim of this study was to detect the attenuating effect of an anti-diabetic drug sitagliptin on porphyromonas gingivalis virulence and inflammatory response in macrophage on titanium discs. Materials and methodsPorphyromonas gingivalis and macrophage were cultured on titanium discs. Antibacterial and antibiofilm activities of sitagliptin were assessed and the morphology of porphyromonas gingivalis were observed by SEM. Bacterial early adhesion, aggregation, hemagglutination, hemolysis and porphyromonas gingivalis virulence factors mRNA expression were assessed to preliminarily investigate the mechanisms of action. Flow cytometry assay, qRT-PCR and Western Blot were used to assess the anti-inflammatory effect of sitagliptin on porphyromonas gingivalis lipopolysaccharide-stimulated macrophage. ResultsThe present study demonstrated the inhibiting effect of sitagliptin on the growth, biofilm, phenotypic behavior and virulence factors of porphyromonas gingivalis and the protective effect on the porphyromonas gingivalis lipopolysaccharide-induced polarization in macrophage. And we also confirmed the anti-inflammatory effect of sitagliptin on the secretion of inflammation-related factors in macrophage by inhibiting the MAPK and AKT signaling pathways. ConclusionsSitagliptin possesses the attenuating effect on porphyromonas gingivalis virulence and inflammatory response in porphyromonas gingivalis lipopolysaccharide-stimulated macrophage on titanium.

Porphyromonas Gingivalis Lipopolysaccharide-induced B Cell Differentiation by Toll-like Receptors 2 and 4

Background: : Porphyromonasgingivalis (P. gingivalis) is a pathogenic bacterium widely present in subgingival plaques of patients with periodontitis. It induces periodontitis with bone loss as its main feature by changing the number and composition of symbiotic microorganisms, as well as inducing the natural immune response of the host. However, the mechanism of the latter remains unclear. Objective:: This study aims to investigate the effect of P. gingivalis lipopolysaccharide (LPS) on regulatory B cells (Breg) in the occurrence and development of periodontitis. Method:: We detected the mRNA levels of IL-10 in B cells under the stimulation of P. gingivalis LPS and/or E. coli LPS, distinguished IL-10-producing cells from different B cell subgroups using flow cytometry. Through toll-like receptor (TLR) knockout mice, the role of TLR2 and TLR4 in this process were also evaluated. Results : Results showed that P. gingivalis stimulated B cells to produce IL-10 via TLR2/4. CD5+B1 subset is the main source of IL-10+Breg cell. Under P. gingivalis LPS stimulation, CD5+IgM+CD93-IL-10+B cell subset increased significantly which was regulated through TLR2/4. Conclusion: The results of this study provides new insights into the immunopathogenic mechanism of P. gingivalis, preliminarily discussed the effect of P. gingivalis on the production of Breg, and present a theoretical foundation for subsequent investigations on the occurrence and development of periodontitis.

STAT1/SOCS1/3 Are Involved in the Inflammation-Regulating Effect of GAS6/AXL in Periodontal Ligament Cells Induced by Porphyromonas gingivalis Lipopolysaccharide In Vitro

Periodontitis involves chronic inflammation of the tissues around the teeth caused by plaque and the corresponding immune response. Growth arrest-specific protein 6 (GAS6) and AXL receptor tyrosine kinase (AXL) are known to be involved in inflammatory diseases, while signal transducer and activator of transcription-1 (STAT1) and suppressor of cytokine signaling (SOCS) are related to inflammatory processes. Moreover, miRNA34a directly targets AXL to regulate the AXL expression. However, the specific roles of GAS6 and AXL in periodontitis remain unclear. This study was designed to explore the effect and mechanism of AXL on the expression of inflammatory cytokines induced by Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in human periodontal ligament cells (hPDLCs). The effects of different concentrations of P. gingivalis LPS on the expression of GAS6/AXL in hPDLCs were observed. Additionally, the effect of LPS on AXL was investigated by transfection of the miRNA34a inhibitor. AXL was knocked down or overexpressed to observe the release of inflammatory cytokines interleukin- (IL-) 8 and IL-6. The results showed that the expression levels of GAS6 and AXL decreased after P. gingivalis LPS infection. Transfection of a miR-34a inhibitor to hPDLCs demonstrated a role of miR-34a in the downregulation of AXL expression induced by LPS. Moreover, AXL knockdown or overexpression influencing the expression of IL-8 and IL-6 was investigated under LPS stimulation. AXL knockdown decreased the expression of STAT1 and SOCS1/3. Overall, these results demonstrate that AXL inhibits the expression of LPS-induced inflammatory cytokines in hPDLCs and that STAT1 and SOCS1/3 are involved in the regulation of inflammation by GAS6/AXL.