Porphyromonas gingivalis enhances the senescence-induced increase of 5-alpha reductase in gingival fibroblasts

Abstract

Objectives: Aging is characterized by chronic inflammatory activity. Senescent cells increase with chronic inflammation and age-related pathologies, including periodontal disease. As a critical regulator of tissue inflammaging, we hypothesized that 5? reductase (5?R) is associated with periodontal disease and bacteria-induced senescence in gingival fibroblasts. Materials and methods: We recruited 36 patients with periodontitis, measured 5?R immunohistochemically before and after periodontal treatment, and compared the expression of 5?R in gingival biopsies from 12 healthy individuals. We then tested the impact of Porphyromonas gingivalis on gingival fibroblasts treated with or without D-galactose-induced cell senescence. We treated primary gingival fibroblasts with D-galactose-supplemented media (0 µM, 50 µM, 100 µM, 1 mM, 10 mM, 50 mM) to induce senescence. The expression of type 1 and type 2 5?R was analyzed with real-time PCR and immunocytochemistry. The levels of IL-6, IL-8, TNF-?, and MCP-1 in fibroblast cultures were evaluated by multiplex immunoassay. Results: In gingival biopsies from patients with periodontal disease, the expression of 5?R was significantly higher than in samples from individuals without periodontal disease (p < 0.001). Periodontal treatment significantly reduced the expression of 5?R in gingival tissues (p < 0.001) to levels comparable in healthy individuals. Gingival fibroblasts exposed to D-galactose-supplemented media had a dose-dependent and significant increase in 5?R expression (p < 0.001). P. gingivalis caused statistically higher type 1 and type 2 5?R expression in gingival fibroblast cells. This effect was exacerbated by the lower doses of D-galactose (p = 0.037). Cells infected with P. gingivalis produced significantly higher levels of IL-6, IL-8, TNF-?, and MCP-1 (p < 0.05) regardless of the D-galactose exposure. Conclusion: The results suggested that 5?R plays a role in periodontal disease and mediates the senescence-induced response to P. gingivalis in gingival fibroblasts. Clinical relevance: Periodontal diseases and aging can increase the production of 5-alpha reductase in the gingival tissue.