Year: 2019
Type: review
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.
Source: Periodontology 2000
DOI: 10.1111/prd.12269
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: National Institute for Health and Care Research, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Environmental Health Sciences, National Institute of Dental and Craniofacial Research, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1135917780, G1243299691, G1527150935, G1691174148, G173303992, G1941623656, Institute for Clinical and Translational Research (UL1), IFI16 is a Periodontitis Modulating Protein, G2818629771, G301743239, G3114902838, G3152385821, G3410686264, G3462919067, GWA for Gene-Environment Interaction Effects Influencing CHD, G4167445418, G4200864717, G457330776, G4824283243, G5074086979, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G567847597, G6195637971, G6548750934, G6552090923, North Carolina Translational and Clinical Science Institute (NC TraCS) KL2, G6902273418, Investigating the role of Tumor Necrosis Factor-Receptor Associated Factor 3 Interacting Protein 2 (TRAF3IP2), a critical adaptor in IL-17 pathway, in periodontal disease, G7372409674, G7470539227, GENOME-WIDE ASSOCIATION STUDY OF PERIODONTAL DISEASE, UNC Center for Environmental Health and Susceptibility, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, SYSTEMIC EFFECTS OF PERIODONTITIS
OpenAlex ID: W2995429038