STING regulates porphyromonas gingivalis lipopolysaccharide-induced pyroptosis and inflammatory response through the NF-κB/NLRP3 signaling pathway in human gingival fibroblasts

Abstract

Objective

The production of reactive oxygen species caused by antimicrobial response during periodontitis leads to the activation of NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis. Stimulator of interferon genes (STING) has been found to be involved in regulating pyroptosis and inflammation in a variety of diseases. The present study aimed to investigate whether STING is involved in Porphyromonas gingivalis lipopolysaccharide (P.g LPS)-stimulated human gingival fibroblasts (HGFs) by regulating pyroptosis and inflammation.

Design

After culturing and identifying HGFs, HGFs were treated with P.g LPS. Constructs of si-STING were transfected into HGFs, which were then stimulated with P.g LPS for 24 h. Subsequently, cell viability, pyroptosis, inflammation, oxidative stress and alterations in the STING/TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/nuclear factor-kappaB (NF-κB)/NLRP3 signalling pathway were detected.

Results

P.g LPS significantly enhanced STING expression in HGFs. Downregulation of STING rescued P.g LPS-enhanced pyroptosis, oxidative stress and inflammation in HGFs. Moreover, STING was found to bind directly to TBK1 to increase IRF3 phosphorylation and nuclear translocation of NF-κB, thus promoting NLRP3 inflammasome activation. Downregulation of STING rescued P.g LPS-enhanced TBK1/IRF3/NF-κB/NLRP3 pathway activation.

Conclusion

STING/TBK1/IRF3/NF-κB/NLRP3 is a key pathway governing pyroptosis, oxidative stress and inflammation of HGFs induced by LPS.