Historical aspects of studies on roles of the inflammasome in the pathogenesis of periodontal diseases

The proinflammatory cytokine interleukin-1 beta (IL-1 beta) is produced as inactive proIL-1 beta and then processed by caspase-1 to become active. In 2002, it was demonstrated that the intracellular multiprotein complex known as the inflammasome functions as a molecular platform to trigger activation of caspase-1. Inflammasomes are known to function as intracellular sensors for a broad spectrum of various pathogen-associated and damage-associated molecular patterns. In 1985, it was demonstrated that Porphyromonas gingivalis, a representative bacterium causing chronic periodontitis, induces IL-1 production by murine peritoneal macrophages. Since then, many studies have suggested that IL-1, particularly IL-1 beta plays key roles in the pathogenesis of periodontal diseases. However, the term inflammasome was not used until the involvement of inflammasomes in periodontal disease was suggested in 2009. Several subsequent studies on the roles of the inflammasome in the pathogenesis of periodontal diseases have been published. Interestingly, two contradictory reports on the modulation of inflammasomes by P.gingivalis have been published. Some papers have described how P.gingivalis activates the inflammasome to produce IL-1 beta whereas some stated that P.gingivalis inhibits inflammasome activation to subvert immune responses. Several lines of evidence have suggested that the inflammasome activation is modulated by periodontopathic bacteria other than P.gingivalis. Hence, studies on the roles of inflammasomes in the pathogenesis of periodontal diseases began only 8 years ago and many pathological roles of inflammasomes remain to be clarified.