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Title: Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics.

Authors: Marchesan, Julie T; Girnary, Mustafa Saadat; Moss, Kevin; Monaghan, Eugenia Timofeev; Egnatz, Grant Joseph; Jiao, Yizu; Zhang, Shaoping; Beck, Jim; Swanson, Karen V

Published In Periodontol 2000, (2020 02)

Abstract: Inflammasomes are a group of multimolecular intracellular complexes assembled around several innate immune proteins. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase-1, which subsequently induces the only known form of secretion of active interleukin-1β and interleukin-18. Although the importance of interleukin-1β in the periodontium is not questioned, the impact of inflammasomes in periodontal disease and its potential for therapeutics in periodontology is still in its very early stages. Increasing evidence in preclinical models and human data strongly implicate the involvement of inflammasomes in a number of inflammatory, autoinflammatory and autoimmune disorders. Here we review: (a) the currently known inflammasome functions, (b) clinical/preclinical data supporting inflammasome involvement in the context of periodontal and comorbid diseases and (c) potential therapies targeting inflammasomes. To clarify further the inflammasome involvement in periodontitis, we present analyses of data from a large clinical study (n = 5809) that measured the gingival crevicular fluid-interleukin-1β and grouped the participants based on current periodontal disease classifications. We review data on 4910 European-Americans that correlate 16 polymorphisms in the interleukin-1B region with high gingival crevicular fluid-interleukin-1β levels. We show that inflammasome components are increased in diseased periodontal tissues and that the caspase-1 inhibitor, VX-765, inhibits ~50% of alveolar bone loss in experimental periodontitis. The literature review further supports that although patients clinically present with the same phenotype, the disease that develops probably has different underlying biological pathways. The current data indicate that inflammasomes have a role in periodontal disease pathogenesis. Understanding the contribution of different inflammasomes to disease development and distinct patient susceptibility will probably translate into improved, personalized therapies.

PubMed ID: 31850638 Exiting the NIEHS site

MeSH Terms: Caspase 1; Gingival Crevicular Fluid; Humans; Inflammasomes*; NLR Family, Pyrin Domain-Containing 3 Protein; Periodontal Diseases*

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