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 of F. nucleatum on human oral tissues and cells has not been fully evaluated. In this study, we aimed to analyze the pathogenic effects of F. nucleatum on human gingival fibroblasts (GFs) and clarify the potential mechanisms. RNA-sequencing analysis confirmed that F. nucleatum significantly altered the gene expression of GF as the stimulation time increased. Cell counting and EdU-labeling assays indicated that F. nucleatum inhibited 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 after F. nucleatum stimulation. Furthermore, we found that the AKT/MAPK and NF-κB signaling pathways were significantly activated by F. nucleatum infection 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 in F. nucleatum-stimulated GFs. These findings suggest that F. nucleatum inhibits 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.

The NF-κB Signaling Pathway, the Microbiota, and Gastrointestinal Tumorigenesis: Recent Advances

“…NLRX1 was shown to negatively modulate inflammatory cytokine IL-8 expression via the transcriptional factor NF-κB in response to F. nucleatum infection (108). Additionally, induction of NF-κB by F. nucleatum infection facilitated ROS generation and production of the proinflammatory cytokines TNF-α and IL-1β (109).…”

Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts

“…Five subjects participating in this program were informed with this research project and signed informed consent according to the Helsinki Declaration of 1975. GFs were cultured and infected with F. nucleatum for 2, 6, 12, 24, and 48 h at the multiplicity of infection (MOI) equal to 100 ( F. nucleatum :cell = 100:1), and then the total RNA of 54 samples from five individuals was extracted and subjected to the RNA-seq analysis according to our previous study (Kang et al, in press). All clean reads were mapped to the reference genome (GRCh38).…”

Minimizing the aerosol-generating procedures in orthodontics in the era of a pandemic: Current evidence on the reduction of hazardous effects for the treatment team and patients

“…16,17 Of the family, Fusobacterium nucleatum has been identified as a bacterium related to pathologic, ophthalmic, and respiratory implications, while also inductive of cellular apoptosis in vivo. 18,19 In addition, it has been reported as related to the launch and progression of periodontitis, or as attenuating attribute of gingival fibroblast mesenchymal cell proliferation. 20 However, the results of checkerboard hybridization techniques should be interpreted with caution as per the exact bacteria species eligible for identification, because such practices are close ended, checked in preselected DNA-probe panels and other pathogens not prespecified might be present within droplet spatters as well.…”