The NF-κB Signalling Regulates the Abnormal Functions of Neutrophils in Severe Periodontal Disease.

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.