Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs

Abstract

AbstractFusobacterium nucleatum(F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built anF. nucleatuminfectious model with human periodontal ligament stem cells (PDLSCs) and showed thatF. nucleatumcould inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. TheF. nucleatumadhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations ofF. nucleatuminfection. NFκB1 and NFκB2 upregulated after 3 h ofF. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects ofF. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms ofF. nucleatumand the host inflammatory response at the early stage ofF. nucleatuminfection.