Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

作者：Julie T. Marchesan, Mustafa Girnary, Kevin Moss, Eugenia Timofeev Monaghan, Grant J. Egnatz, Yizu Jiao, Shaoping Zhang, Jim Beck, Karen V. Swanson · 发表于：Periodontology 2000 · 年份：2019 · DOI：10.1111/prd.12269 · 被引用次数：154 · 研究领域：Inflammasome and immune disorders、Streptococcal Infections and Treatments、Immune Response and Inflammation

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...