Pro-resolving mediators in the regulation of periodontal disease

Abstract

Periodontitis is an inflammatory disease of the supporting structures of the dentition that is initiated by bacterial that form a biofilm on the surface of the teeth. The pathogenesis of the disease is a result of complex interactions between the biofilm and the host response that results in dysbiosis of the microbiome and dysregulation of the inflammatory response. Current data suggest that the excess inflammation associated with periodontitis is due to a failure of resolution of inflammation pathways. In this review, the relationship between inflammation and microbial dysbiosis is examined in the context of pro-inflammation and pro-resolution mediators and their ability to modify the course of disease. The impact of local oral inflammation on systemic inflammation and the relationship of periodontitis to other inflammatory diseases, including type 2 diabetes and cardiovascular disease is reviewed. Active resolvers of inflammation, including the lipoxins and resolvins, show great promise as therapeutics for the treatment of periodontitis and other inflammatory diseases.

Salivary levels of specialized pro‐resolving lipid mediators as indicators of periodontal health/disease status

“…The most immediate application is in the investigation of patients who meet clinical and immunological criteria for developing periodontitis by using high‐throughput salivary biomarker validation tools for rapid chair‐side testing (Brinkmann et al, ; Korte & Kinney, ; Van Dyke, ). In addition, the authors expect that the confirmation of involvement of this pathway in periodontal diseases will be of importance for the management of periodontitis by inducing SPMs as novel drug targets to extend the pharmaceutical armamentarium to combat chronic inflammation, thus controlling periodontal inflammation, reversing pathologic changes related to the human microbiome, therefore promoting tissue regeneration and return to homeostasis (Grover et al, ; Hasturk & Kantarci, ; Tarannum & Faizuddin, ; Van Dyke, , ).…”

“…Although it has been postulated that the dysregulation of SPMs or the dysfunction of resolution pathways may be factors of the immune response that could influence the destructive activity of periodontitis in response to bacterial challenge (Elabdeen et al, ; Hasturk & Kantarci, ; Van Dyke, ; Van Dyke & Serhan, ) nothing is known regarding the salivary levels of these SPMs and their association with the degree of periodontal breakdown. Since understanding the role of homeostatic mechanisms is essential to stop and prevent inflammatory tissue damage and salivary analysis is an efficient method for the biomonitoring of markers associated with periodontitis (Gröschl, ), this study aimed to determine using immunoenzymatic methods, if salivary levels of LXA4, PD1, RvE1 and MaR1 might constitute a reflection of periodontal health/disease status.…”

Epigenetic and inflammatory events in experimental periodontitis following systemic microbial challenge

“…This resolution of inflammation in mice occurred during the healing period when the stimulus was withdrawn. This could be due to elevated endogenous inflammation‐resolving factors such as developmental endothelial locus‐1 protein (DEL‐1) and/or resolvins (Hasturk & Kantarci, ; Maekawa et al, ; Shin et al, ; Van Dyke, ). On the other hand, at the end of the 42‐day period, we observed a consistent bone loss in the group where the microbial gavage was used.…”

Osteoimmunology: Inflammatory osteolysis and regeneration of the alveolar bone

“…Cytokines and lipid mediators not only provoke, they also trigger the resolution of inflammation thereby support tissue regeneration (Schett & Neurath, ; Van Dyke, ). For example, the lack of anti‐inflammatory cytokines pushes tissue destruction.…”

“…Nanoparticles containing the lipoxin analog benzo‐lipoxin A4 promote regeneration of hard and soft tissues irreversibly lost due to periodontitis in a pig model (Van Dyke et al., ). Thus, pro‐inflammatory lipid mediators not only reduce inflammation but can also support tissue regeneration (Van Dyke, ). Apart from cytokines, chemokines and lipid mediators, also proteases control inflammatory osteolysis.…”