GroEL triggers NLRP3 inflammasome activation through the TLR/NF-κB p-p65 axis in human periodontal ligament stem cells

Acta Biochim Biophys Sin (Shanghai). 2024 Apr 10;56(9):1340-1351. doi: 10.3724/abbs.2024050.

Abstract

The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1β and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.

Keywords: GroEL; NF-κB signaling; NLRP3 inflammasome; TLR; periodontitis.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chaperonin 60* / genetics
  • Chaperonin 60* / metabolism
  • Humans
  • Inflammasomes* / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Periodontal Ligament* / cytology
  • Periodontal Ligament* / metabolism
  • Periodontal Ligament* / microbiology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Stem Cells* / metabolism
  • Toll-Like Receptor 2* / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Transcription Factor RelA / metabolism

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Chaperonin 60
  • Inflammasomes
  • NLRP3 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • TLR2 protein, human
  • Interleukin-1beta
  • Interleukin-18
  • TLR4 protein, human

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (No. 32270193 to C.L. and No. 81771047 to J.C.) and the Sichuan Science and Technology Innovation Talent Project (No. 2022JDRC0044).