Fusobacterium nucleatumFacilitates Apoptosis, ROS Generation, and Inflammatory Cytokine Production by Activating AKT/MAPK and NF-κB Signaling Pathways in Human Gingival Fibroblasts

Abstract

Fusobacterium nucleatum(F. nucleatum) plays key roles in the initiation and progression of periodontitis. However, the pathogenic effect ofF. nucleatumon human oral tissues and cells has not been fully evaluated. In this study, we aimed to analyze the pathogenic effects ofF. nucleatumon human gingival fibroblasts (GFs) and clarify the potential mechanisms. RNA-sequencing analysis confirmed thatF. nucleatumsignificantly altered the gene expression of GF as the stimulation time increased. Cell counting and EdU-labeling assays indicated thatF. nucleatuminhibited GF proliferation and promoted cell apoptosis in a time- and dose-dependent manner. In addition, cell apoptosis, intracellular reactive oxygen species (ROS) generation, and proinflammatory cytokine production were dramatically elevated afterF. nucleatumstimulation. Furthermore, we found that the AKT/MAPK and NF-κB signaling pathways were significantly activated byF. nucleatuminfection and that a large number of genes related to cellular proliferation, apoptosis, ROS, and inflammatory cytokine production downstream of AKT/MAPK and NF-κB signaling pathways were significantly altered inF. nucleatum-stimulated GFs. These findings suggest thatF. nucleatuminhibits GF proliferation and promotes cell apoptosis, ROS generation, and inflammatory cytokine production partly by activating the AKT/MAPK and NF-κB signaling pathways. Our study opens a new window for understanding the pathogenic effects of periodontal pathogens on the host oral system.