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Published in: Inflammation Research 1/2017

01-01-2017 | Original Research Paper

Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease

Authors: Yohei Yamaguchi, Tomoko Kurita-Ochiai, Ryoki Kobayashi, Toshihiko Suzuki, Tomohiro Ando

Published in: Inflammation Research | Issue 1/2017

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Abstract

Objective

Porphyromonas gingivalis is involved in the pathogenesis of chronic inflammatory periodontal disease. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of chronic inflammation. We investigated a possible association between the inflammasome in gingival inflammation and bone loss induced by P. gingivalis infection using NLRP3-deficient mice.

Methods

Wild-type and NLRP3-deficient mice were injected orally with P. gingivalis. We assessed alveolar bone loss, expression of pro-interleukin (IL)-1β, pro-IL-18, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) in gingival tissue, as well as IL-1β, IL-18, and IL-6 production and caspase-1 activity in peritoneal macrophages.

Results

Porphyromonas gingivalis challenge significantly increased alveolar bone loss; gingival gene expression of pro-IL-1β, pro-IL-18, and RANKL; production of IL-1β, IL-18, and IL-6; and caspase-1 activity in peritoneal macrophages of wild-type mice, but did not affect NLRP3-deficient mice. Meanwhile, OPG mRNA expression in gingival tissue and peritoneal IL-6 production were significantly higher in NLRP3-knockout mice.

Conclusions

Porphyromonas gingivalis activated innate immune cells via the NLRP3 inflammasome. These results suggest that the NLRP3 inflammasome, followed by a response from the IL-1 family, is critical in periodontal disease induced by wild-type P. gingivalis challenge via sustained inflammation.
Literature
1.
go back to reference Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clin Microbiol Rev. 2001;14(4):727–52.CrossRefPubMedPubMedCentral Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clin Microbiol Rev. 2001;14(4):727–52.CrossRefPubMedPubMedCentral
2.
go back to reference Burt B, Research S. Therapy Committee of the American Academy of P. Position paper: epidemiology of periodontal diseases. J Periodontol. 2005;76(8):1406–19.CrossRef Burt B, Research S. Therapy Committee of the American Academy of P. Position paper: epidemiology of periodontal diseases. J Periodontol. 2005;76(8):1406–19.CrossRef
3.
go back to reference Olsen I. Update on bacteraemia related to dental procedures. Transfus Apher Sci. 2008;39(2):173–8.CrossRefPubMed Olsen I. Update on bacteraemia related to dental procedures. Transfus Apher Sci. 2008;39(2):173–8.CrossRefPubMed
4.
go back to reference Imatani T, Kato T, Okuda K. Production of inflammatory cytokines by human gingival fibroblasts stimulated by cell-surface preparations of Porphyromonas gingivalis. Oral Microbiol Immunol. 2001;16(2):65–72.CrossRefPubMed Imatani T, Kato T, Okuda K. Production of inflammatory cytokines by human gingival fibroblasts stimulated by cell-surface preparations of Porphyromonas gingivalis. Oral Microbiol Immunol. 2001;16(2):65–72.CrossRefPubMed
5.
go back to reference Morandini AC, Sipert CR, Ramos-Junior ES, Brozoski DT, Santos CF. Periodontal ligament and gingival fibroblasts participate in the production of TGF-beta, interleukin (IL)-8 and IL-10. Braz Oral Res. 2011;25(2):157–62.PubMed Morandini AC, Sipert CR, Ramos-Junior ES, Brozoski DT, Santos CF. Periodontal ligament and gingival fibroblasts participate in the production of TGF-beta, interleukin (IL)-8 and IL-10. Braz Oral Res. 2011;25(2):157–62.PubMed
6.
go back to reference Yucel-Lindberg T, Brunius G. Epidermal growth factor synergistically enhances interleukin-8 production in human gingival fibroblasts stimulated with interleukin-1beta. Arch Oral Biol. 2006;51(10):892–8.CrossRefPubMed Yucel-Lindberg T, Brunius G. Epidermal growth factor synergistically enhances interleukin-8 production in human gingival fibroblasts stimulated with interleukin-1beta. Arch Oral Biol. 2006;51(10):892–8.CrossRefPubMed
7.
go back to reference Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, McIntosh ML, Alsam A, Kirkwood KL, Lambris JD, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497–506.CrossRefPubMedPubMedCentral Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, McIntosh ML, Alsam A, Kirkwood KL, Lambris JD, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497–506.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Becker CE, O’Neill LA. Inflammasomes in inflammatory disorders: the role of TLRs and their interactions with NLRs. Semin Immunopathol. 2007;29(3):239–48.CrossRefPubMed Becker CE, O’Neill LA. Inflammasomes in inflammatory disorders: the role of TLRs and their interactions with NLRs. Semin Immunopathol. 2007;29(3):239–48.CrossRefPubMed
10.
go back to reference Kummer JA, Broekhuizen R, Everett H, Agostini L, Kuijk L, Martinon F, van Bruggen R, Tschopp J. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J Histochem Cytochem. 2007;55(5):443–52.CrossRefPubMed Kummer JA, Broekhuizen R, Everett H, Agostini L, Kuijk L, Martinon F, van Bruggen R, Tschopp J. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J Histochem Cytochem. 2007;55(5):443–52.CrossRefPubMed
11.
go back to reference Pontillo A, Girardelli M, Agostinis C, Masat E, Bulla R, Crovella S. Bacterial LPS differently modulates inflammasome gene expression and IL-1beta secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells. Reprod Sci. 2013;20(5):563–6.CrossRefPubMed Pontillo A, Girardelli M, Agostinis C, Masat E, Bulla R, Crovella S. Bacterial LPS differently modulates inflammasome gene expression and IL-1beta secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells. Reprod Sci. 2013;20(5):563–6.CrossRefPubMed
12.
go back to reference Park E, Na HS, Song YR, Shin SY, Kim YM, Chung J. Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection. Infect Immun. 2014;82(1):112–23.CrossRefPubMedPubMedCentral Park E, Na HS, Song YR, Shin SY, Kim YM, Chung J. Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection. Infect Immun. 2014;82(1):112–23.CrossRefPubMedPubMedCentral
13.
go back to reference Zheng F, Xing S, Gong Z, Xing Q. NLRP3 inflammasomes show high expression in aorta of patients with atherosclerosis. Heart Lung Circ. 2013;22(9):746–50.CrossRefPubMed Zheng F, Xing S, Gong Z, Xing Q. NLRP3 inflammasomes show high expression in aorta of patients with atherosclerosis. Heart Lung Circ. 2013;22(9):746–50.CrossRefPubMed
14.
go back to reference Yamaguchi Y, Kurita-Ochiai T, Kobayashi R, Suzuki T, Ando T. Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis. Pathog Dis. 2015;73(4). doi:10.1093/femspd/ftv011. Yamaguchi Y, Kurita-Ochiai T, Kobayashi R, Suzuki T, Ando T. Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis. Pathog Dis. 2015;73(4). doi:10.​1093/​femspd/​ftv011.
15.
go back to reference Bostanci N, Belibasakis GN. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett. 2012;333(1):1–9.CrossRefPubMed Bostanci N, Belibasakis GN. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett. 2012;333(1):1–9.CrossRefPubMed
16.
go back to reference Kanneganti TD, Ozoren N, Body-Malapel M, Amer A, Park JH, Franchi L, Whitfield J, Barchet W, Colonna M, Vandenabeele P, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature. 2006;440(7081):233–6.CrossRefPubMed Kanneganti TD, Ozoren N, Body-Malapel M, Amer A, Park JH, Franchi L, Whitfield J, Barchet W, Colonna M, Vandenabeele P, et al. Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature. 2006;440(7081):233–6.CrossRefPubMed
17.
go back to reference Klausen B, Evans RT, Sfintescu C. Two complementary methods of assessing periodontal bone level in rats. Scand J Dent Res. 1989;97(6):494–9.PubMed Klausen B, Evans RT, Sfintescu C. Two complementary methods of assessing periodontal bone level in rats. Scand J Dent Res. 1989;97(6):494–9.PubMed
18.
go back to reference Kobayashi R, Kono T, Bolerjack BA, Fukuyama Y, Gilbert RS, Fujihashi K, Ruby J, Kataoka K, Wada M, Yamamoto M, et al. Induction of IL-10-producing CD4+ T-cells in chronic periodontitis. J Dent Res. 2011;90(5):653–8.CrossRefPubMedPubMedCentral Kobayashi R, Kono T, Bolerjack BA, Fukuyama Y, Gilbert RS, Fujihashi K, Ruby J, Kataoka K, Wada M, Yamamoto M, et al. Induction of IL-10-producing CD4+ T-cells in chronic periodontitis. J Dent Res. 2011;90(5):653–8.CrossRefPubMedPubMedCentral
20.
go back to reference Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13(6):397–411.CrossRefPubMed Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13(6):397–411.CrossRefPubMed
21.
go back to reference Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol. 2008;79(8 Suppl):1569–76.CrossRefPubMed Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol. 2008;79(8 Suppl):1569–76.CrossRefPubMed
22.
go back to reference Ruscitti P, Cipriani P, Carubbi F, Liakouli V, Zazzeroni F, Di Benedetto P, Berardicurti O, Alesse E, Giacomelli R. The role of IL-1beta in the bone loss during rheumatic diseases. Mediators Inflamm. 2015;2015:782382.CrossRefPubMedPubMedCentral Ruscitti P, Cipriani P, Carubbi F, Liakouli V, Zazzeroni F, Di Benedetto P, Berardicurti O, Alesse E, Giacomelli R. The role of IL-1beta in the bone loss during rheumatic diseases. Mediators Inflamm. 2015;2015:782382.CrossRefPubMedPubMedCentral
23.
go back to reference Dai SM, Nishioka K, Yudoh K. Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in rheumatoid arthritis: comparison with IL1 beta and tumour necrosis factor alpha. Ann Rheum Dis. 2004;63(11):1379–86.CrossRefPubMedPubMedCentral Dai SM, Nishioka K, Yudoh K. Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in rheumatoid arthritis: comparison with IL1 beta and tumour necrosis factor alpha. Ann Rheum Dis. 2004;63(11):1379–86.CrossRefPubMedPubMedCentral
24.
go back to reference Polzer K, Joosten L, Gasser J, Distler JH, Ruiz G, Baum W, Redlich K, Bobacz K, Smolen JS, van den Berg W, et al. Interleukin-1 is essential for systemic inflammatory bone loss. Ann Rheum Dis. 2010;69(1):284–90.CrossRefPubMed Polzer K, Joosten L, Gasser J, Distler JH, Ruiz G, Baum W, Redlich K, Bobacz K, Smolen JS, van den Berg W, et al. Interleukin-1 is essential for systemic inflammatory bone loss. Ann Rheum Dis. 2010;69(1):284–90.CrossRefPubMed
25.
go back to reference Netea MG, van de Veerdonk FL, van der Meer JW, Dinarello CA, Joosten LA. Inflammasome-independent regulation of IL-1-family cytokines. Annu Rev Immunol. 2015;33:49–77.CrossRefPubMed Netea MG, van de Veerdonk FL, van der Meer JW, Dinarello CA, Joosten LA. Inflammasome-independent regulation of IL-1-family cytokines. Annu Rev Immunol. 2015;33:49–77.CrossRefPubMed
26.
go back to reference Lukens JR, Gross JM, Calabrese C, Iwakura Y, Lamkanfi M, Vogel P, Kanneganti TD. Critical role for inflammasome-independent IL-1beta production in osteomyelitis. Proc Natl Acad Sci USA. 2014;111(3):1066–71.CrossRefPubMedPubMedCentral Lukens JR, Gross JM, Calabrese C, Iwakura Y, Lamkanfi M, Vogel P, Kanneganti TD. Critical role for inflammasome-independent IL-1beta production in osteomyelitis. Proc Natl Acad Sci USA. 2014;111(3):1066–71.CrossRefPubMedPubMedCentral
27.
go back to reference Babur C, Ozcan G, Cebi DU, Pervane B, Ozdemir B, Yucel A, Biri AA, Babur C. Gingival crevicular fluid levels of osteoprotegerin (OPG) in premenopausal and postmenopausal women with or without chronic periodontitis. J Dent. 2012;40(5):364–71.CrossRefPubMed Babur C, Ozcan G, Cebi DU, Pervane B, Ozdemir B, Yucel A, Biri AA, Babur C. Gingival crevicular fluid levels of osteoprotegerin (OPG) in premenopausal and postmenopausal women with or without chronic periodontitis. J Dent. 2012;40(5):364–71.CrossRefPubMed
28.
go back to reference Tang H, Mattheos N, Yao Y, Jia Y, Ma L, Gong P. In vivo osteoprotegerin gene therapy preventing bone loss induced by periodontitis. J Periodontal Res. 2015;50(4):434–43.CrossRefPubMed Tang H, Mattheos N, Yao Y, Jia Y, Ma L, Gong P. In vivo osteoprotegerin gene therapy preventing bone loss induced by periodontitis. J Periodontal Res. 2015;50(4):434–43.CrossRefPubMed
29.
go back to reference McGeough MD, Pena CA, Mueller JL, Pociask DA, Broderick L, Hoffman HM, Brydges SD. Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse models. J Immunol. 2012;189(6):2707–11.CrossRefPubMedPubMedCentral McGeough MD, Pena CA, Mueller JL, Pociask DA, Broderick L, Hoffman HM, Brydges SD. Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse models. J Immunol. 2012;189(6):2707–11.CrossRefPubMedPubMedCentral
Metadata
Title
Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease
Authors
Yohei Yamaguchi
Tomoko Kurita-Ochiai
Ryoki Kobayashi
Toshihiko Suzuki
Tomohiro Ando
Publication date
01-01-2017
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 1/2017
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-016-0992-4

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