Isoliquiritigenin Alleviates P. Gingivalis-Lps/atp-induced Pyroptosis by Inhibiting NF-κB/ NLRP3/GSDMD Signals in Human Gingival Fibroblasts.

Objective: To investigate whether pyroptosis is induced by Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)/ adenosine triphosphate (ATP) through NF-kappa B/NLRP3/GSDMD signaling in human gingival fibroblasts (HGFs) and whether isoliquiritigenin (ISL) alleviates pyroptosis by inhibition of NF-kappa B/NLRP3/ GSDMD signals. Design: Periodontitis was optimally simulated using a combination of P. gingivalis-LPS and ATP. The expression levels of genes and proteins of NF-kappa B, NLRP3 inflammasome, GSDMD, and IL-1 ss was characterized by qRT-PCR, western blotting and ELISA. The 2',7'-dichlorodihydrofluorescein diacetate fluorescence probe was used to determine the intracellular ROS level. Hoechst 33342 and PI double staining, cytotoxicity assay, and caspase-1 activity assay were used to confirm the influence of ISL on pyroptosis in P. gingivalis-LPS/ATP-treated HGFs. Results: P. gingivalis-LPS/ATP stimulation significantly promoted expression of NF-kappa B, the NLRP3 inflammasome, GSDMD, and IL-1 ss at gene and protein levels. The proportion of membrane-damaged cells, caspase-1 activity, and the release of lactate dehydrogenase (LDH) were also elevated. However, pretreatment with ISL observably suppressed these effects. Conclusions: P. gingivalis-LPS/ATP induced pyroptosis in HGFs by activating NF-kappa B/NLRP3/GSDMD signals and ISL attenuated P. gingivalis-LPS/ATP-induced pyroptosis by inhibiting these signals. This evidence may provide a new direction for the treatment of periodontitis.