Abstract
OBJECTIVES: To explore the regulatory mechanism of neutrophils in severe periodontitis (PDs), given their link to periodontal inflammation progression (PDs). METHODS: Single-cell RNA-seq and bulk RNA transcriptome data from GEO were analysed using ClusterProfiler for DEG enrichment, hdWGCNA to identify neutrophil-linked module genes, pySCENIC for specific regulons, co-immunostaining for protein expression, and LPS-stimulated human gingival neutrophils with real-time PCR for inflammatory factors. RESULTS: Neutrophils in PDs showed activated inflammatory response and NF-κB signalling, acting as key mediators in cell-cell communication. hdWGCNA identified 7 modules, with transcription factor Nrf2 highly specific to PD neutrophils. NFKB1 was upregulated, and NF-κB inhibition reduced LPS-induced IL2, IL8, and TGFβ production. CONCLUSIONS: Neutrophils are central to PDs, with activated NF-κB pathways. Clinically, targeting NF-κB reduces gingivitis-induced inflammatory cytokines. CLINICAL SIGNIFICANCE: Specific inhibition of the NF-κB signalling pathway can reduce the expression of Porphyromonas gingivalis LPS-induced inflammatory cytokines.