title: Expression and regulation of the NALP3 inflammasome complex in periodontal diseases.
abstract: 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.
authors: Department of Periodontology, University College London Eastman Dental Institute, London WC1X 8LD, UK. n.bostanci@eastman.ucl.ac.uk
authors: N
authors: N
authors: Bostanci
authors: G
authors: G
authors: Emingil
authors: B
authors: B
authors: Saygan
authors: O
authors: O
authors: Turkoglu
authors: G
authors: G
authors: Atilla
authors: M A
authors: MA
authors: Curtis
authors: G N
authors: GN
authors: Belibasakis
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D055113:Chronic Periodontitis / Q000276:immunology / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005881:Gingiva / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016966:Porphyromonas gingivalis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; D012333:RNA, Messenger