2023 年 21 巻 4 号 p. 147-155
Individuals with Down syndrome(DS)are prone to periodontitis. No studies have focused on mRNA expression of a pro-inflammatory cytokine, IL-1β and an anti-inflam matory cytokine, IL-37 in gingival fibroblasts(GFs)derived from individuals with DS (DGFs). We cultured GFs derived from non-DS individuals(NGFs)and DGFs with outer membrane vesicles from Porphyromonas gingivalis(P-OMVs). IL-1β and IL-37 mRNA expression was quantified using real-time PCR. Extracellular signal-regulated kinase(ERK)1/2 phosphorylation was performed by western blotting. We also analyzed the effect of an ERK1/2 inhibitor on IL-1β and IL-37 mRNA expression in GFs. Furthermore, we examined the influence of recombinant IL-37(rIL-37)on the cellular response of GFs. We quantified mRNA expression of IL-8 using real-time PCR and measured IL-8 productions in culture medium by an enzyme-linked immunosorbent assay. IL-1β mRNA expression and phosphorylated-ERK1/2 expression were significantly higher in P-OMVs-stimulated DGFs than in NGFs. In contrast, IL-37 mRNA expression was significantly lower in P-OMV-stimulated DGFs than in NGFs. P-OMVs-induced IL-1β and IL-37 mRNA expression in NGFs was reduced by an ERK1/2 inhibitor, while P-OMVs-induced IL-37 mRNA expression was not reduced by an ERK1/2 inhibitor in DGFs. P-OMVs-induced IL-8 mRNA expression and protein production were decreased by rIL-37 in both NGF and DGFs. It is considered that the imbalance of pro- and anti-inflammatory responses via ERK1/2 in DGFs may cause severe periodontal inflammation in DS. In addition, IL-37 may be a key mediator of the anti-inflammatory response in DGFs. These results provide insights into the therapeutic potential of targeting anti-inflammatory factors for severe periodontal inflammation in DS.