2021 Volume 42 Issue 1 Pages 43-52
It is well known that individuals with Down syndrome (DS) have a high prevalence of severe periodontitis, but the reasons have not been clear. Porphyromonas gingivalis (P.g), which is known as the most important periodontopathic bacteria, is an asaccharolytic anaerobe that needs metabolic energy from peptides and amino acids. Therefore, P.g produces several types of proteolytic enzymes which cause periodontal tissue destruction. There are few reports about the effect of aminoacyl histidine dipeptidase, PepD. PepD is a proteolytic enzyme frequently of type Ⅱ P.g, which is detected in high amounts in patients with severe periodontitis. In this study, we examined whether PepD acts as a pathogen of severe periodontitis in DS or not. Gingival fibroblasts derived from Non-DS (NGF) and from DS (DGF) were stimulated with recombinant PepD (rPepD). After incubation, we measured the production of inflammatory mediators and analyzed their mRNA expressions. In addition, NGF and DGF were subjected to cell scratch assay for cell proliferation and migration. The productions of interleukin (IL)-6 and IL-8 in DGF stimulated with rPepD were significantly higher than those in NGF. The mRNA expressions of IL-6, IL-8 and chemokine (C-C motif) ligand 20 (CCL20) in DGF stimulated with rPepD were significantly higher than those in NGF. In addition, nuclear factor kappa B (NF-κB) p65 activity was observed strongly in DGF with rPepD compared to NGF. Therefore, it is considered that the high expressions of inflammatory mediators in DGF with rPepD were induced via the pathway of NF-κB. Cell proliferation and increase in growth factors such as Ki67, epidermal growth factor (EGF) and fibroblast growth factor (FGF) are necessary for termination of the inflammatory phase. DGF cell proliferation was found to be significantly faster than that of NGF. The mRNA expressions of Ki67, EGF and FGF in DGF with rPepD were significantly higher than those in NGF. Furthermore, EGF and FGF mRNA expressions were significantly higher in DGF without rPepD compared to NGF. It is considered that these phenomena induced the persistent inflammation via feedback regulation of those growth factors to the cells. Further studies are needed for clarification.
