1. Academic Validation
  2. Caspase-3 and gasdermin E mediate macrophage pyroptosis in periodontitis

Caspase-3 and gasdermin E mediate macrophage pyroptosis in periodontitis

  • J Periodontal Res. 2023 Oct 26. doi: 10.1111/jre.13197.
Xiangru Gao 1 2 Shuhan Li 1 2 Wenxuan Wang 3 Xiangyan Zhang 4 Xinbo Yu 1 Chun Fan 1 Wei Li 1 Caixiu Yang 1 2 Lei Wang 1 Qiuxia Ji 1 2
Affiliations

Affiliations

  • 1 Department of Periodontology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • 2 School of Stomatology, Qingdao University, Qingdao, China.
  • 3 Department of Stomatology, Qingdao West Coast New Area Central Hospital, Qingdao, China.
  • 4 Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Abstract

Background and objectives: Periodontitis is a chronic inflammatory disease linked to Pyroptosis, an inflammatory cell death process. Macrophages are essential for maintaining microenvironment homeostasis, which is crucial for periodontal health. This study explores the mechanisms underlying the relationship between macrophage Pyroptosis and periodontitis.

Methods: Expression of the Pyroptosis marker gasdermin E (GSDME) and the macrophage surface marker CD68 was examined by immunofluorescence double staining in healthy and periodontitis gingival tissues. In an in vitro Pyroptosis model, RAW264.7 cells were irritated using Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) after treatment with either a nuclear factor kappa-B (NF-κB) agonist or inhibitor. The mRNA and protein levels of NF-κB, Caspase-3, GSDME, and interleukin-1β (IL-1β) were evaluated through qRT-PCR, western blotting, and ELISA techniques.

Results: GSDME and CD68 were heavily elevated in inflamed gingival tissues compared to healthy tissues and co-localized in the same region. Furthermore, exposure to P. gingivalis-LPS resulted in a significant upregulation of NF-κB, Caspase-3, GSDME, and IL-1β at both the mRNA and protein levels in RAW264.7 cells. NF-κB Agonist or inhibitor pretreatment enhanced or inhibited these effects.

Conclusions: GSDME-mediated macrophage Pyroptosis is implicated in periodontitis. Based on in vitro experiments, P. gingivalis-LPS causes Pyroptosis in RAW264.7 cells through the Caspase-3/GSDME pathway. Furthermore, NF-κB regulates this pyroptotic pathway.

Keywords

GSDME; NF-κB; macrophage; periodontitis; pyroptosis.

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