Expression and regulation of the NALP3 inflammasome complex in periodontal diseases

Clin Exp Immunol. 2009 Sep;157(3):415-22. doi: 10.1111/j.1365-2249.2009.03972.x.


Periodontitis is an infectious process characterized by inflammation affecting the supporting structures of the teeth. Porphyromonas gingivalis is a major oral bacterial species implicated in the pathogenesis of periodontitis. Processing of interleukin (IL)-1 family cytokines is regulated by an intracellular innate immune response system, known as the NALP3 [nacht domain-, leucine-rich repeat-, and pyrin domain (PYD)-containing protein 3] inflammasome complex. The aim of the present study was to investigate by quantitative real-time polymerase chain reaction (PCR) the mRNA expression of NALP3, its effector molecule apoptosis associated speck-like protein (ASC), its putative antagonist NLRP2 (NLR family, PYD-containing protein 2), IL-1beta and IL-18 (i) in gingival tissues from patients with gingivitis (n = 10), chronic periodontitis (n = 18), generalized aggressive periodontitis (n = 20), as well as in healthy subjects (n = 20), (ii) in vitro in a human monocytic cell line (Mono-Mac-6), in response to P. gingivalis challenge for 6 h. The clinical data indicate that NALP3 and NLRP2, but not ASC, are expressed at significantly higher levels in the three forms of inflammatory periodontal disease compared to health. Furthermore, a positive correlation was revealed between NALP3 and IL-1beta or IL-18 expression levels in these tissues. The in vitro data demonstrate that P. gingivalis deregulates the NALP3 inflammasome complex in Mono-Mac-6 cells by enhancing NALP3 and down-regulating NLRP2 and ASC expression. In conclusion, this study reveals a role for the NALP3 inflammasome complex in inflammatory periodontal disease, and provides a mechanistic insight to the host immune responses involved in the pathogenesis of the disease by demonstrating the modulation of this cytokine-signalling pathway by bacterial challenge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • CARD Signaling Adaptor Proteins
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Cell Line
  • Chronic Periodontitis / immunology
  • Chronic Periodontitis / metabolism*
  • Cytoskeletal Proteins / genetics
  • Female
  • Gene Expression Regulation*
  • Gingiva / immunology
  • Gingiva / metabolism*
  • Gingiva / microbiology
  • Humans
  • Interleukin-18 / genetics
  • Interleukin-1beta / genetics
  • Male
  • Middle Aged
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Porphyromonas gingivalis / physiology*
  • RNA, Messenger / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Young Adult


  • CARD Signaling Adaptor Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Interleukin-18
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • PYCARD protein, human
  • RNA, Messenger