Double-Edged Sword Effect of Pyroptosis: The Role of Caspase-1/-4/-5/-11 in Different Levels of Apical Periodontitis

Biomolecules. 2022 Nov 8;12(11):1660. doi: 10.3390/biom12111660.

Abstract

The study was to investigate the effect of canonical and noncanonical pyroptosis in apical periodontitis. Proteins' profiles of human apical periodontitis tissue were analyzed by label-free proteomics. Immunofluorescence was used to detect proteins related to pyroptosis in human apical periodontitis tissues and experimental apical periodontitis models. A dual experimental apical periodontitis model with both smaller (mandible) and larger (maxilla) bone lesions was established. THP-1-derived macrophages were stimulated with P. gingivalis lipopolysaccharide in vitro with or without the caspase-1/-4/-5 inhibitor Ac-FTDL-CMK. Propidium iodide staining, lactic dehydrogenase release and Western blot were applied to evaluate cell death and the protein expression. Caspase-1/-4/-5 were expressed in human apical periodontitis tissues. Caspase-1/-11 were involved in bone loss in experimental apical periodontitis. Caspase-1/-11 inhibitors reduced bone loss in larger lesions (maxilla) but accelerated bone loss in smaller lesions (mandible). Caspase-1/-4/-5 inhibitors also showed double-edged sword effects on propidium iodide staining and lactic dehydrogenase release in vitro. The expression of cleaved-caspase-1/-4/-5, mature interluekin-1β and gasdermin D N-terminal domain increased in THP-1-derived macrophages after lipopolysaccharide stimulation but decreased after treatment with Ac-FTDL-CMK. Pyroptosis contributed to apical periodontitis and excited a double-edged sword effect in inducing bone loss in vivo and cell death in vitro.

Keywords: apical periodontitis; bone loss; caspase-1/-4/-5/-11; pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 1 / metabolism
  • Caspases / metabolism
  • Humans
  • Lipopolysaccharides / pharmacology
  • Oxidoreductases
  • Periapical Periodontitis*
  • Propidium / pharmacology
  • Pyroptosis* / physiology

Substances

  • Lipopolysaccharides
  • Propidium
  • Caspase 1
  • Caspases
  • Oxidoreductases

Grants and funding

This research was funded by the National Natural Science Foundation of China [81970948 and U20A20365] and Natural Science Foundation of Sichuan Province of China [2022NSFSC0613].