Involvement of ferroptosis in Porphyromonas gingivalis lipopolysaccharide-stimulated periodontitis in vitro and in vivo.

Abstract

Ferroptosis is associated with multiple inflammatory diseases. Periodontitis is an inflammatory disease mainly caused by oral opportunistic pathogens. However, the ferroptosis-periodontitis relationship has not been thoroughly described. We here analyzed whether ferroptosis is involved in periodontitis. Human gingival fibroblasts (HGFs) were stimulated with P.gingivalis-LPS and ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and changes in mitochondrial morphology, ferroptosis-related factors, and inflammation levels were detected. After the rat experimental periodontitis model was established, changes in ferroptosis-related factors and inflammation levels were re-evaluated in the same manner. Porphyromonas gingivalis-LPS-induced mitochondrial shrinkage, an increase in mitochondrial membrane density, and upregulation of reactive oxygen species in HGFs. The expression of prostaglandin-endoperoxide synthase 2, transferrin receptor 1, and malondialdehyde and inflammation levels were upregulated, whereas the expression of solute carrier family seven member 11, glutathione peroxidase 4, superoxide dismutase, and glutathione were downregulated. Fer-1 attenuated these aforementioned changes and inflammation levels induced by P.gingivalis-LPS. The in vivo experiment results were consistent with the in vitro experiment results. Ferroptosis is involved in inflammatory processes in HGFs upon P.gingivalis-LPS stimulation. Ferroptosis is observed in the gingival tissue of periodontitis rats.