Ammonia Induced Macrophage Death Aggravates Periodontitis

Aim or purpose: Ammonia accumulation disrupts immune homeostasis and induces cell death. however, its role in the progression of periodontitis remains largely unclear. This study aimed to investigate whether ammonia-induced macrophage death contributes to the progression of periodontitis. Materials and methods: Gingival crevicular fluid (GCF) was collected from periodontitis patients and healthy controls to quantify ammonia levels. An in vitro inflammatory model was established using LPS-stimulated rat bone marrow-derived macrophages. NH₄Cl was subsequently used to induce intracellular ammonia accumulation. Cell proliferation and viability were assessed via CCK-8 and live/dead staining. The expression of ammonia transporters (RHAG, RHBG, RHCG), autophagy markers (LC3, P62), and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) was assessed using qRT-PCR, Western blotting, and ELISA. All procedures were approved by the institutional Ethics Committee. Results: GCF from periodontitis patients showed significantly higher ammonia concentrations than the controls. NH₄Cl treatment led to intracellular ammonia buildup, increased expression of ammonia transporters, impaired autophagic flux, reduced cell proliferation, and elevated cytokine expression under inflammatory conditions. Conclusions: These findings indicate that ammonia induces a distinct form of macrophage cell death associated with autophagy disruption, potentially contributing to the progression of periodontitis. Targeting ammonia metabolism in macrophages may provide a novel therapeutic strategy for periodontal disease.