Aggregatibacter actinomycetemcomitansによるインフラマソームの活性化

Aggregatibacter actinomycetemcomitans

北海道歯学会

北海道歯学雑誌

Inflammasome is an intracellular sensor that regulates the production of IL-1β, which is one of the inflammatory cytokines with diverse biological activities. Recently, inflammasome is intensively investigated as a clue to clarify pathogenesis of many inflammatory diseases that are known to be associated with IL-1β. In periodontitis, IL-1β is known to play an important role in the pathogenesis. However, few reports on the association between periodontitis and inflammasome have been obtained, although some periodontopathogenic bacteria induced production of IL-1β exist. In this study we investigated whether Aggregatibacter actinomycetemcomitans, a major pathogen of aggressive periodontitis, as well as systemic diseases such as infectious endocarditis, induce the activation of inflammasome in a murine dendritic cell line like XS106 cells. Futher investigation was carried out,to clarify its pathogenic roles in periodontitis. Stimulation of XS106 cells with live and heat killed cells of A. actinomycetemcomitans induced production of IL-1β, whereas the cultute supernatant did not. The IL-1β production-inducing activity of live and heat killed cells was significantly inhibited by Z-YVAD-FMK and Z-VAD-FMK, which are inhibitors for caspase 1 and all caspases, respectively. In addition, the activity was significantly attenuated by the decrease of mRNAs of caspase-1 and NLRP3. Furthermore, both heat-killed and live cells induced necrosis-like cell death in XS106 cells, which is considered to be pyroptosis because of its accompanying the production of IL-1β. Thus, these results suggest that A. actinomycetemcomitans activates NLRP3 inflammasome in murine dendritic cells producing IL-1β, which is released extracellularly by pyroptosis.