The role of inflammasomes in periodontal disease and pathogenesis
Main Article Content
Keywords
Inflammasome, NLRP3, periodontal disease, periodontal pathogen, IL-1β
Abstract
Inflammasomes are complex cellular structures that play crucial roles in the pathogenesis of periodontal disease. Inflammasomes are proteins that sense microbial pathogens in the host and trigger an inflammatory response. This response is vital for combating infection but can also damage tissue if inflammation is not controlled. Several studies have reviewed the role of inflammasomes in periodontal disease. In periodontal disease, inflammasome activation has been linked to the release of pro-inflammatory cytokines, which can lead to tissue destruction and periodontal damage. The term "inflammasome" was coined by Jurg Tschopp in 2002. Recently, significant research has focused on activating inflammasomes and their roles in disease processes. The NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes have been identified as essential. Inflammasomes are a group of proteins that are part of the innate immune system and play a role in the pathogenesis of periodontal diseases. They are activated by bacteria, which leads to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Periodontitis is triggered by these cytokines, leading to increased inflammation and tissue destruction. This review aimed to examine how these inflammasomes contribute to periodontitis pathogenesis.
References
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26. Bergsbaken, T.; Fink, S.L.; Cookson, B.T. Pyroptosis: Host Cell Death and Inflammation. Nat. Rev. Microbiol. 2009, 7,99–109.
27. O’Brien, M.; Moehring, D.; Muñoz-Planillo, R.; Núñez, G.; Callaway, J.; Ting, J.; Scurria, M.; Ugo, T.; Bernad, L.; Cali, J.; et al. A Bioluminescent Caspase-1 Activity Assay Rapidly Monitors Inflammasome Activation in Cells. J. Immunol. Methods 2017, 447,1–13.
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29. Tan, Y.; Chen, J.; Jiang, Y.; Chen, X.; Li, J.; Chen, B.; Gao, J. The anti-periodontitis action of metformin via targeting NLRP3 inflammasome. Archives of Oral Biology 2020,114, 104692.
30. Murakami, T.; Takahata, Y.; Hata, K.; Nishimura, R. Role of interleukin-1 and inflammasomes in oral disease. J. Oral Biosci. 2020,62, 242–248.
31. Bostanci, N.; Emingil, G.; Saygan, B.; Turkoglu, O.; Atilla, G.; Curtis, M.A.; Belibasakis, G.N. Expression, and regulation of the NALP3 inflammasome complex in periodontal diseases. Clin. Exp. Immunol. 2009,157,415–422.
32. Isaza-Guzmán, D.M.; Medina-Piedrahíta, V.M.; Gutiérrez-Henao, C.; Tobón-Arroyave, S.I. Salivary Levels of NLRP3 Inflammasome-Related Proteins as Potential Biomarkers of Periodontal Clinical Status. J. Periodontol. 2017, 88, 1329–1338.
33. Detert, J.; Pischon, N.; Burmester, G.R.; Buttgereit, F. The association between rheumatoid arthritis and periodontal disease. Arthritis Res. Ther. 2010,12, 218.
34. Mealey, B.L.; Ocampo, G.L. Diabetes mellitus and periodontal disease. Periodontol. 2000 2007, 44, 127–153.
35. Singhrao, S.K.; Harding, A.; Poole, S.; Kesavalu, L.; Crean, S. Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer’s Disease. Mediat. Inflamm. 2015, 2015,137357.
36. Zang, Y.; Song, JH.; Oh, SH.; Kim, JW.; Lee, MN.; Piao, X.; Yang, JW.; Kim, OS.; Kim, TS.; Kim, SH.; Koh, JT. Targeting NLRP3 Inflammasome Reduces Age-Related Experimental Alveolar Bone Loss. 2020,99,1287-1295.
37. Galler, KM.; Weber, M.; Korkmaz, Y.; Widbiller, M.; Feuerer , M. Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues. Int J Mol Sci 2021, 22,1480.
38. Jang, JH.; Shin, HW.; Lee, JM.; Lee, HW.; Kim, EC.; Park, SH. An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp. Mediators Inflamm. 2015, 2015,794143.
39. Isaza-Guzmán, D.M.; Medina-Piedrahíta, V.M.; Gutiérrez-Henao, C.; Tobón-Arroyave, S.I. Salivary levels of NLRP3 inflammasome-related proteins as potential biomarkers of periodontal clinical status. J. Periodontol. 2017, 88,1329–1338.
40. Fernanda, R G.; Rocha Andrea E.; Delitto Joao, A.; Souza, CD.; Laura, A.; González-Maldonado, G.; Wallet SM.; and Junior, CS. Relevance of Caspase-1 and Nlrp3 Inflammasome on Inflammatory Bone Resorption in A Murine Model of Periodontitis. Scientific reports 2020,10, 7823.
41. Zhao1, D.; Wu ,Y.; Zhuang ,J.; Xu, C.; Zhang, F. Activation of NLRP1 and NLRP3 inflammasomes contributed to cyclic stretch-induced pyroptosis and release of IL-1β in human periodontal ligament cells. Oncotarget 2016, 7, 68292 – 68302.
42. Hou, L.;Ye, Y.; Gou, H.; Tang, H.; Zhou, Y.; Xu, X.; Xu, Y. A20 inhibits periodontal bone resorption and NLRP3-mediated M1 macrophage polarization. Exp Cell Res. 2022, 418,113264.
43. Chen J, Wei J, Wang F, et al. Inflammasomes in chronic periodontitis and periodontal disease. Crit Rev Immunol. 2019;39(3):197-215.
44. Li X, Liu H, Zhang L, et al. The inflammasome pathway in periodontitis: pathogenesis and therapeutic opportunities. Mol Oral Microbiol. 2021;36(3):83-97.
45. Jiao Y, Darzi Y, Tawaratsumida K, et al. Induction of bone loss by pathobiont-mediated Nod1 signaling in the oral cavity. Cell Host Microbe. 2013;13(5):595-601.
46. Huang H, Ostberg N, Lu L, et al. Targeting inflammation and the microbiome in chronic disease: lessons from periodontitis. Adv Oral Biol. 2020; 5:100084.
47. Guo C, et al. NLRP3 inflammasome activation contributes to the pathogenesis of periodontitis. J Dent Res. 2014;93(4):372-81.
48. Zhang Q, et al. NLRP3 inflammasome expression and signaling in human periodontal ligament cells. Int J Clin Exp Pathol. 2014;7(8):4914-20.
49. Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157(5):1013-22.
50. Shao B, Li C, Yao Y, Wu Y, Wu F, Yuan Y, et al. NLRP3 inflammasome regulates Th17 differentiation in rheumatoid arthritis. Clin Immunol. 2015;157(2):114-120.
2. Peres, MA.; Macpherson, LMD.; Weyant, RJ.; Daly, B.; Venturelli, R.; Mathur, MR., et al. Oral diseases: a global public health challenge. Lancet. 2019,394,249-60
3. Kinane, DF.; Stathopoulou, PG.; Papapanou, PN. Periodontal diseases. Nat Rev Dis Primers. 2017,3,17038.
4. Acharya, A.; VanWormer, JJ.; Waring, SC.; Miller, AW.; Fuehrer, JT.; Nycz, GR. Regional epidemiologic assessment of prevalent periodontitis using an electronic health record system. Am J Epidemiol. 2013,177,700-7.
5. Genco, RJ.; Borgnakke, WS. Diabetes as a potential risk for periodontitis: association studies. Periodontol 2000. 2020,83,40-5.
6. Kamer, AR.; Craig, RG.; Niederman, R.; Fortea, J.; de Leon, MJ. Periodontal disease as a possible cause for Alzheimer's disease. Periodontol 2000. 2020,83,242-71
7. Marchesan JT, Girnary MS, Moss K, Monaghan ET, Egnatz GJ, Jiao Y, Zhang S, Beck J, Swanson, KV. Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics. Periodontol 2000. 2020, 82,93-114.
8. Feng, Y.; Huang, X. Methodology for Comprehensive Detection of Pyroptosis. Methods Mol. Biol. 2021, 2255, 149–157.
9. Miao, E.A.; Leaf, I.A.; Treuting, P.M.; Mao, D.P.; Dors, M.; Sarkar, A.; Warren, S.E.; Wewers, M.D.; Aderem, A. Caspase-1-Induced Pyroptosis Is an Innate Immune Effector Mechanism against Intracellular Bacteria. Nat. Immunol. 2010, 11, 1136–1142.
10. Martinon, F.; Burns, K.; Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL‐beta. Mol Cell. 2002,10,417‐426.
11. Yu, C.; Zhang, C.; Kuang, Z.; Zheng, Q. The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification. Inflammation 2021,44, 434–449.
12. Strowig, T.; Henao-Mejia, J.; Elinav, E. et al. Inflammasomes in health and disease. Nature 2012, 481, 278–286.
13. Zhang, Y.; Dong, Z.;Song, W. NLRP3 inflammasome as a novel therapeutic target for Alzheimer's disease. Signal Transduct Target Ther. 2020, 5, 37.
14. Strowig, T.; Henao-Mejia, J.; Elinav, E.; Flavell, R. Inflammasomes in health and disease. NATURE 2012, 481,278-286.
15. Schroder, K.; Tschopp, J. The Inflammasomes. Cell 2010, 140,821-32.
16. SM, Man T-D Kanneganti. Converging roles of caspases in inflammasome activation, cell death and innate immunity at Rev Immunol.2016,17,7-21.
17. Ben-Sasson, S.Z.; Hu-Li, J.; Quiel, J.; Cauchetaux, S.; Ratner, M.; Shapira, I.; Dinarello, C.A.; Paul, W.E. IL-1 acts on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc. Natl. Acad. Sci. USA 2009, 106,7119–7124.
18. Aral, K.; Milward, MR.; Kapila, Y.; Berdeli, A.; Cooper, PR. Inflammasomes and their regulation in periodontal disease: A review. J Periodontal Res. 2020,55,473-487.
19. T. W. , Oates.; D.; T, Graves.; D. L., Cochran. Clinical, radiographic and biochemical assessment of IL-1/TNF-α antagonist inhibition of bone loss in experimental periodontitis Clin Periodontol 2002, 29,137-43.
20. Delaleu N and Bickel M: Interleukin-1 beta and interleukin-18: Regulation and activity in local inflammation. Periodontol 2000. 2004; 35:42–52.
21. Rana, A.; Kaur, A.; Faraz, F.; Tandon, S."Targeting inflammasomes: A possible therapeutic approach for periodontal disease (Review)". World Academy of Sciences Journal 2021,3,50.
22. Ding, PH.; Yang, MX.; Wang, NN. ; Jin, LJ.; Dong, Y.; Cai, X.; Chen, LL. Porphyromonas gingivalis-Induced NLRP3 Inflammasome Activation and Its Downstream Interleukin-1β Release Depend on Caspase-4. Front. Microbiol.
2020, 11, 1881.
23. Lu, W.L.; Song, D.Z.; Yue, J.L.; Wang, T.T.; Zhou, X.D.; Zhang, P.; Zhang, L.; Huang, D.M. NLRP3 Inflammasome May Regulate Inflammatory Response of Human Periodontal Ligament Fibroblasts in an Apoptosis-Associated Speck-like Protein Containing a CARD (ASC)-Dependent Manner. Int. Endod. J. 2017, 50, 967–975.
24. Juna, KH.; Junga JY.; Choia, BK. Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia induce cell death and release of endogenous danger signals. Archives of Oral Biology 2017, 73, 72–78
25. Simon, A.; van der Meer, J.W.M. Pathogenesis of Familial Periodic Fever Syndromes or Hereditary Autoinflammatory Syndromes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 292, R86–R98.
26. Bergsbaken, T.; Fink, S.L.; Cookson, B.T. Pyroptosis: Host Cell Death and Inflammation. Nat. Rev. Microbiol. 2009, 7,99–109.
27. O’Brien, M.; Moehring, D.; Muñoz-Planillo, R.; Núñez, G.; Callaway, J.; Ting, J.; Scurria, M.; Ugo, T.; Bernad, L.; Cali, J.; et al. A Bioluminescent Caspase-1 Activity Assay Rapidly Monitors Inflammasome Activation in Cells. J. Immunol. Methods 2017, 447,1–13.
28. Yamaguchi, Y.; Kurita-Ochiai, T.; Kobayashi, R. et al. Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease. Inflamm. Res.2017, 66,59–65.
29. Tan, Y.; Chen, J.; Jiang, Y.; Chen, X.; Li, J.; Chen, B.; Gao, J. The anti-periodontitis action of metformin via targeting NLRP3 inflammasome. Archives of Oral Biology 2020,114, 104692.
30. Murakami, T.; Takahata, Y.; Hata, K.; Nishimura, R. Role of interleukin-1 and inflammasomes in oral disease. J. Oral Biosci. 2020,62, 242–248.
31. Bostanci, N.; Emingil, G.; Saygan, B.; Turkoglu, O.; Atilla, G.; Curtis, M.A.; Belibasakis, G.N. Expression, and regulation of the NALP3 inflammasome complex in periodontal diseases. Clin. Exp. Immunol. 2009,157,415–422.
32. Isaza-Guzmán, D.M.; Medina-Piedrahíta, V.M.; Gutiérrez-Henao, C.; Tobón-Arroyave, S.I. Salivary Levels of NLRP3 Inflammasome-Related Proteins as Potential Biomarkers of Periodontal Clinical Status. J. Periodontol. 2017, 88, 1329–1338.
33. Detert, J.; Pischon, N.; Burmester, G.R.; Buttgereit, F. The association between rheumatoid arthritis and periodontal disease. Arthritis Res. Ther. 2010,12, 218.
34. Mealey, B.L.; Ocampo, G.L. Diabetes mellitus and periodontal disease. Periodontol. 2000 2007, 44, 127–153.
35. Singhrao, S.K.; Harding, A.; Poole, S.; Kesavalu, L.; Crean, S. Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer’s Disease. Mediat. Inflamm. 2015, 2015,137357.
36. Zang, Y.; Song, JH.; Oh, SH.; Kim, JW.; Lee, MN.; Piao, X.; Yang, JW.; Kim, OS.; Kim, TS.; Kim, SH.; Koh, JT. Targeting NLRP3 Inflammasome Reduces Age-Related Experimental Alveolar Bone Loss. 2020,99,1287-1295.
37. Galler, KM.; Weber, M.; Korkmaz, Y.; Widbiller, M.; Feuerer , M. Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues. Int J Mol Sci 2021, 22,1480.
38. Jang, JH.; Shin, HW.; Lee, JM.; Lee, HW.; Kim, EC.; Park, SH. An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp. Mediators Inflamm. 2015, 2015,794143.
39. Isaza-Guzmán, D.M.; Medina-Piedrahíta, V.M.; Gutiérrez-Henao, C.; Tobón-Arroyave, S.I. Salivary levels of NLRP3 inflammasome-related proteins as potential biomarkers of periodontal clinical status. J. Periodontol. 2017, 88,1329–1338.
40. Fernanda, R G.; Rocha Andrea E.; Delitto Joao, A.; Souza, CD.; Laura, A.; González-Maldonado, G.; Wallet SM.; and Junior, CS. Relevance of Caspase-1 and Nlrp3 Inflammasome on Inflammatory Bone Resorption in A Murine Model of Periodontitis. Scientific reports 2020,10, 7823.
41. Zhao1, D.; Wu ,Y.; Zhuang ,J.; Xu, C.; Zhang, F. Activation of NLRP1 and NLRP3 inflammasomes contributed to cyclic stretch-induced pyroptosis and release of IL-1β in human periodontal ligament cells. Oncotarget 2016, 7, 68292 – 68302.
42. Hou, L.;Ye, Y.; Gou, H.; Tang, H.; Zhou, Y.; Xu, X.; Xu, Y. A20 inhibits periodontal bone resorption and NLRP3-mediated M1 macrophage polarization. Exp Cell Res. 2022, 418,113264.
43. Chen J, Wei J, Wang F, et al. Inflammasomes in chronic periodontitis and periodontal disease. Crit Rev Immunol. 2019;39(3):197-215.
44. Li X, Liu H, Zhang L, et al. The inflammasome pathway in periodontitis: pathogenesis and therapeutic opportunities. Mol Oral Microbiol. 2021;36(3):83-97.
45. Jiao Y, Darzi Y, Tawaratsumida K, et al. Induction of bone loss by pathobiont-mediated Nod1 signaling in the oral cavity. Cell Host Microbe. 2013;13(5):595-601.
46. Huang H, Ostberg N, Lu L, et al. Targeting inflammation and the microbiome in chronic disease: lessons from periodontitis. Adv Oral Biol. 2020; 5:100084.
47. Guo C, et al. NLRP3 inflammasome activation contributes to the pathogenesis of periodontitis. J Dent Res. 2014;93(4):372-81.
48. Zhang Q, et al. NLRP3 inflammasome expression and signaling in human periodontal ligament cells. Int J Clin Exp Pathol. 2014;7(8):4914-20.
49. Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157(5):1013-22.
50. Shao B, Li C, Yao Y, Wu Y, Wu F, Yuan Y, et al. NLRP3 inflammasome regulates Th17 differentiation in rheumatoid arthritis. Clin Immunol. 2015;157(2):114-120.
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Apr 11, 2023
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Nada Hashim, Rasha Babiker, Riham Mohammed, Mohammed Mustahsen Rehman, & Bakri Gobara. (2023). The role of inflammasomes in periodontal disease and pathogenesis. Journal of Population Therapeutics and Clinical Pharmacology, 30(6), 226–238. https://doi.org/10.47750/jptcp.2023.30.06.030
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