Author(s): Pradeep Koppolu, Rasheed Abdulsalam

Email(s): drpradeepk08@gmail.com

DOI: 10.52711/0974-360X.2022.00313   

Address: Pradeep Koppolu, Rasheed Abdulsalam*
Faculty of Dentistry, Lincoln University College, Malaysia.
*Corresponding Author

Published In:   Volume - 15,      Issue - 4,     Year - 2022


ABSTRACT:
The NLRP3 inflammasome is a vital component of the innate immune system that mediates caspase-1 activation and secretion of the proinflammatory cytokines, namely interleukins (IL-1/IL-18), in retort to microbial infection such as periodontal pathogens. Secretion of IL-1ß is a major component of periodontal tissue inflammation and a crucial cause of periodontal disease. The conversion of pro-IL-1ß into its biologically active form is controlled by inflammasomes such as NLRP3. Nevertheless, uncontrolled NLRP3 activation may cause several inflammatory disorders such as Alzheimer’s disease, periodontitis, diabetes, and atherosclerosis. NLRP3 activation may be caused due to various stimuli, leading to multiple molecular and cellular events. Drugs targeting the various steps in these events may provide a solution to the aberrant NLRP3 activation. In this review, we have investigated the various mechanisms of NLLRP3 activation and the various drugs which have exhibited its inhibition.


Cite this article:
Pradeep Koppolu, Rasheed Abdulsalam. Role of the NLRP3 Inflammasome in Periodontal Disease: A Tour d'horizon. Research Journal of Pharmacy and Technology. 2022; 15(4):1870-6. doi: 10.52711/0974-360X.2022.00313

Cite(Electronic):
Pradeep Koppolu, Rasheed Abdulsalam. Role of the NLRP3 Inflammasome in Periodontal Disease: A Tour d'horizon. Research Journal of Pharmacy and Technology. 2022; 15(4):1870-6. doi: 10.52711/0974-360X.2022.00313   Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2022-15-4-79


REFERENCES:
1.    Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global Prevalence of Periodontal Disease and Lack of Its Surveillance. Scientific World Journal. 2020 May 28;2020:2146160. doi: 10.1155/2020/2146160.
2.    Shaju JP, Zade RM, Das M. Prevalence of periodontitis in the Indian population: A literature review. J Indian Soc Periodontol. 2011;15:29–34. DOI: 10.4103/0972-124X.82261
3.    Song B, Zhou T, Yang WL, Liu J, Shao LQ. Programmed cell death in periodontitis: recent advances and future perspectives. Oral Dis 2017;23:609-619. DOI: 10.1186/s11671-016-1704-2
4.    Marchesan JT, Girnary MS, Moss K, Monaghan ET, Egnatz GJ, Jiao Y, et al. Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics. Periodontology 2000. 2020;82:93–114. DOI: 10.1111/prd.12269
5.    Kelley N, Jeltema D, Duan Y, He Y. The NLRP3 Inflammasome: An Overview of  Mechanisms of Activation and Regulation. Int. J. Mol. Sci. 2019; 20: 3328; doi:10.3390/ijms20133328.
6.    Franchi, L.; Eigenbrod, T.; Muñoz-Planillo, R.; Nuñez, G. The Inflammasome: A Caspase-1 Activation Platform Regulating Immune Responses and Disease Pathogenesis. Nat. Immunol. 2009;10: 241. DOI:10.1111/j.1600-065X.2008.00730.x
7.    Dinarello, C.A. Immunological and Inflammatory Functions of the Interleukin-1 Family. Annu. Rev. Immunol. 2009; 27: 519–550. DOI: 10.1146/annurev.immunol.021908.132612
8.    Wang, Li., Hauenstein, A.V. The NLRP3 inflammosome: Mechanism of action, role in disease and therapies. Molecular Aspects of Medicine. 2020, 76, 100889. https://doi.org/10.1016/j.mam.2020.100889
9.    Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitorsCell Death and Disease 2019;10:128 https://doi.org/10.1038/s41419-019-1413-8.
10.    Guo, H.; Callaway, J.B.; Ting, J.P.-Y. Inflammasomes: Mechanism of action, role in disease, and therapeutics. Nat. Med. 2015, 21, 677–687. DOI: 10.1038/nm.3893
11.    Vajjhala, P.R.; Mirams, R.E.; Hill, J.M. Multiple binding sites on the pyrin domain of ASC protein allow self-association and interaction with NLRP3 protein. J. Biol. Chem. 2012;287: 41732–41743. DOI:10.1074/jbc.M112.381228
12.    Green JP, Yu S, Martín-Sánchez F, et al. Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming. Proc Natl Acad Sci USA. 2018;115(40):E9371-E9380. https://doi.org/10.1073/pnas.1812744115
13.    Hara H, Tsuchiya K, Kawamura I, et al. Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity. Nat Immunol 2013;14(12):1247-1255. DOI: 10.1038/ni.2749
14.    Bauernfeind, F.G.; Horvath, G.; Stutz, A.; Alnemri, E.S.; MacDonald, K.; Speert, D.; Fernandes-Alnemri, T.; Wu, J.; Monks, B.G.; Fitzgerald, K.A.; et al. Cutting Edge: NF-kB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression. J. Immunol 2009; 183: 787–791. DOI: 10.4049/jimmunol.0901363
15.    Gurung, P.; Anand, P.K.; Malireddi, R.K.S.; Walle, L.V.; Opdenbosch, N.V.; Dillon, CP et al. FADD and Caspase-8 Mediate Priming and Activation of the Canonical and Noncanonical Nlrp3 Inflammasomes. J. Immunol. 2014; 192:1835–1846. DOI: 10.4049/jimmunol.1302839
16.    Allam, R.; Lawlor, K.E.; Yu, E.C.-W.; Mildenhall, A.L.; Moujalled, D.M.; Lewis, R.S et al. Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Rep. 2014; 15: 982–990. https://doi.org/10.1002/eji.201545655
17.    Lemmers, B.; Salmena, L.; Bidère, N.; Su, H.; Matysiak-Zablocki, E.; Murakami, K.; et al. Essential Role for Caspase-8 in Toll-like Receptors and NFB Signaling. J. Biol. Chem. 2007;282,: 7416–7423. doi: 10.1074/jbc.M606721200
18.    Ranjan, K.; Pathak, C. FADD regulates NF-kB activation and promotes ubiquitination of cFLIPL to induce apoptosis. Sci. Rep. 2016; 6:22787. doi: 10.1038/srep22787
19.    Juliana, C.; Fernandes-Alnemri, T.; Kang, S.; Farias, A.; Qin, F.; Alnemri, E.S. Non-transcriptional Priming and Deubiquitination Regulate NLRP3 Inflammasome Activation. J. Biol. Chem. 2012; 287: 36617–36622. DOI: 10.1074/jbc.m112.407130
20.    Schroder, K.; Sagulenko, V.; Zamoshnikova, A.; Richards, A.A.; Cridland, J.A.; Irvine, K.M, et al. Acute lipopolysaccharide priming boosts inflammasome activation independently of inflammasome sensor induction. Immunobiology 2012; 217: 1325–1329. https://doi.org/10.1016/j.imbio.2012.07.020
21.    Lin, K.-M.; Hu, W.; Troutman, T.D.; Jennings, M.; Brewer, T.; Li, X, et al. IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation. Proc. Natl. Acad. Sci. USA 2014; 111: 775–780. DOI: 10.1073/pnas.1320294111
22.    Song, N.; Liu, Z.-S.; Xue,W.; Bai, Z.-F.;Wang, Q.-Y.; Dai, J et al. NLRP3 Phosphorylation Is an Essential Priming Event for Inflammasome Activation. Mol. Cell 2017; 68: 185–197.e6. DOI:https://doi.org/10.1016/j.molcel.2017.08.017
23.    Zhong, Z.; Liang, S.; Sanchez-Lopez, E.; He, F.; Shalapour, S.; Lin, X et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 2018; 560: 198–203. DOI: 10.1038/s41586-018-0372-z
24.    Muñoz-Planillo, R.; Kua, P.; Martínez-Colón, G.; Smith, B.L.; Rajendiran, T.M.; Núñez, G. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 2013; 38: 1142–1153. DOI: 10.1016/j.immuni.2013.05.016
25.    Pétrilli, V.; Papin, S.; Dostert, C.; Mayor, A.; Martinon, F.; Tschopp, J. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Dier. 2007; 14: 1583–1589. DOI: 10.1038/sj.cdd.4402195
26.    Clapham, D.E. Calcium signaling. Cell 2007; 131: 1047–1058. DOI: 10.1016/j.cell.2007.11.028
27.    Murakami, T.; Ockinger, J.; Yu, J.; Byles, V.; McColl, A.; Hofer, A.M.; Horng, T. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc. Natl. Acad. Sci. USA 2012;109: 11282–11287. https://doi.org/10.1073/pnas.1117765109
28.    Verhoef, P.A.; Kertesy, S.B.; Lundberg, K.; Kahlenberg, J.M.; Dubyak, G.R. Inhibitory effects of chloride on the activation of caspase-1, IL-1beta secretion, and cytolysis by the P2X7 receptor. J. Immunol. Baltim. Md 1950 2005; 175: 7623–7634. DOI: 10.4049/jimmunol.175.11.7623
29.    Tang, T.; Lang, X.; Xu, C.;Wang, X.; Gong, T.; Yang,Y.; Cui, J.; Bai, L.;Wang, J.; Jiang,W.; et al. CLICs-dependent chloride eux is an essential and proximal upstream event forNLRP3 inflammasome activation. Nat. Commun 2017;8:202. doi: 10.1038/s41467-017-00227-x.
30.    Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011 May;12(5):408-15. doi: 10.1038/ni.2022.
31.    Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, Ramanujan VK, Wolf AJ, Vergnes L, Ojcius DM, Rentsendorj A, Vargas M, Guerrero C, Wang Y, Fitzgerald KA, Underhill DM, Town T, Arditi M. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012 Mar 23;36(3):401-14. doi: 10.1016/j.immuni.2012.01.009.
32.    Bauernfeind F, Bartok E, Rieger A, Franchi L, Núñez G, Hornung V. Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol. 2011 Jul 15;187(2):613-7. doi: 10.4049/jimmunol.1100613.
33.    Hornung, V.; Bauernfeind, F.; Halle, A.; Samstad, E.O.; Kono, H.; Rock, K.L.; Fitzgerald, K.A.; Latz, E. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 2008,;9: 847–856. doi: 10.1038/ni.1631
34.    Codolo, G.; Plotegher, N.; Pozzobon, T.; Brucale, M.; Tessari, I.; Bubacco, L.; de Bernard, M. Triggering of Inflammasome by Aggregated–Synuclein, an Inflammatory Response in Synucleinopathies. PLoS ONE 2013; 8: e55375. https://doi.org/10.1371/journal.pone.0055375
35.    Orlowski, G.M.; Colbert, J.D.; Sharma, S.; Bogyo, M.; Robertson, S.A.; Rock, K.L. Multiple Cathepsins Promote Pro-IL-Synthesis and NLRP3-Mediated IL-1 Activation. J. Immunol. Baltim. Md 1950 2015; 195: 1685–1697. DOI: 10.4049/jimmunol.1500509
36.    Jyotsna Sanjeevi, Priyalochana Gajendran. Role of Interleukin 1 in serum in Chronic Periodontitis -A Review. Research J. Pharm. and Tech 2017; 10(11): 4090-4092. DOI: 10.5958/0974-360X.2017.00741.7
37.    Py, B. F., Kim, M. S., Vakifahmetoglu-Norberg, H. & Yuan, J. Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. Mol. Cell 2013; 49: 331–338. doi:10.1016/j.molcel.2012.11.009
38.    Hunter, T. The age of crosstalk: phosphorylation, ubiquitination, and beyond. Mol. Cell 2007; 28: 730–738. DOI: 10.1016/j.molcel.2007.11.019
39.    Baker PJ, Boucher D, Bierschenk D. et al. NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. Eur. J. Immunol. 2015;45: 2918–2926. DOI: 10.1002/eji.201545655
40.    Yang, J., Zhao, Y. & Shao, F. Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Curr. Opin. Immunol.2015; 32:78–83. doi: 10.1016/j.coi.2015.01.007
41.    Gaidt, M. M. & Hornung, V. Alternative inflammasome activation enables IL-1β release from living cells. Curr. Opin. Immunol. 2017;44: 7–13. doi: 10.1016/j.coi.2016.10.007.
42.    R. Sai Pavithra, Sheeja Varghese. Gingival Tissue Level of Interleukin-1 in Diabetic Patient with Chronic Periodontitis. Research J. Pharm. and Tech 2017; 10(12): 4442-4444. DOI: 10.5958/0974-360X.2017.00818.6
43.    Frial Gemeel Abd. Polymorphism of IL-4 (-590) and IL-6 (-174) is not associated with Chronic Periodontitis in Babylonian Population. Research J. Pharm. and Tech. 2018; 11(1): 275-280. doi: 10.5958/0974-360X.2018.00051.3.
44.    Nowarski, R, Jackson R, Gagliani N et al. Epithelial IL-18 equilibrium controls barrier function in colitis. Cell 2015; 163: 1444–1456. doi: 10.1016/j.cell.2015.10.072.
45.    Coll, R. C. et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 2015;21: 248. doi: 10.1038/nm.3806.
46.    Jiang, H. et al. Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J. Exp. Med. 2017;214: 3219–3238. doi: 10.1084/jem.20171419.
47.    Yogesh N. Gholse, Manjusha P. Yeole, Shailju G. Gurunani. Inflammasomes: Types and Activation. Research J. Pharm. and Tech. 7(6): June, 2014; Page 695-703
48.    Akansha Devandra Camabala, Priyalochana Gajendran. Role of Interleukin 1 in Gingival Tissues in Chronic Periodontitis -A Review. Research J Pharm and Tech 2017; 10(9): 3185-3187. DOI: 10.5958/0974-360X.2017.00566.2
49.    Frial Gemeel Abd. Polymorphism of IL-4 (-590) and IL-6 (-174) is not associated with Chronic Periodontitis in Babylonian Population. Research J Pharm and Tech. 2018; 11(1): 275-280. DOI: 10.5958/0974-360X.2018.00051.3
50.    Divyadharsini V, Sankari M. Effect of Smoking on Interleukin- 1 and Reactive Oxygen Species in Periodontitis. Research J. Pharm. and Tech. 2018; 11(3): 1247-1250 DOI: 10.5958/0974-360X.2018.00232.9
51.    Koppolu P, Durvasula S, Palaparthy R, Rao M, Sagar V, Reddy SK, Lingam S. Estimate of CRP and TNF-alpha level before and after periodontal therapy in cardiovascular disease patients. Pan Afr Med J. 2013 Jul 10;15:92. doi: 10.11604/pamj.2013.15.92.2326.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

0.38
2018CiteScore
 
56th percentile
Powered by  Scopus


SCImago Journal & Country Rank


Recent Articles




Tags


Not Available