Isoliquiritigenin alleviates P. gingivalis-LPS/ATP-induced pyroptosis by inhibiting NF-κB/ NLRP3/GSDMD signals in human gingival fibroblasts

  • Int Immunopharmacol. 2021 Dec;101(Pt B):108338. doi: 10.1016/j.intimp.2021.108338.
Xiaofang Lv  1 ,  Chun Fan  2 ,  Zhongxin Jiang  3 ,  Wenxuan Wang  1 ,  Xu Qiu  1 ,  Qiuxia Ji  4
Affiliations
  • 1. Department of Periodontology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China; School of Stomatology, Qingdao University, Qingdao, Shandong, China.
  • 2. Department of Periodontology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
  • 3. Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
  • 4. Department of Periodontology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address: [email protected].
PMID: 34794890 DOI: 10.1016/j.intimp.2021.108338
Abstract

Objective: To investigate whether Pyroptosis is induced by Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS)/ adenosine triphosphate (ATP) through NF-κB/NLRP3/GSDMD signaling in human gingival fibroblasts (HGFs) and whether isoliquiritigenin (ISL) alleviates Pyroptosis by inhibition of NF-κB/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-κB, NLRP3 inflammasome, GSDMD, and IL-1β 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-κB, the NLRP3 inflammasome, GSDMD, and IL-1β 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-κB/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.

Keywords
GSDMD; Isoliquiritigenin; NF-κB; NLRP3 inflammasome; Periodontitis; Pyroptosis.
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