Thesis or Dissertation Activation of NLRP3 inflammasome in dendritic cells and macrophages by Mycoplasma salivarium

杉山, 正博

The proinflammatory cytokine IL-1β plays crucial roles in the pathogenesis of periodontal disease. IL-1β is produced after processing of pro-IL-1β by caspase-1, which is activated by the multiprotein complex consisting of NLR, an adaptor protein and procaspase-1, called an the inflammasome. Mycoplasma salivarium, human oral microbial flora, preferentially inhabits the gingival sulcus and is considered to play an etiological role in periodontal diseases. As a first step to clarify the etiological role of the organism in periodontal diseases, this study was designed to clarify whether it induces production of IL-1β by innate immune cells such as dendritic cells or macrophages by using M. pneumoniae, which is known to induce production of IL-1β by human macrophages, as a positive control. It was found that both live and heat-killed cells of M. salivarium induced production of IL-1β by the murine dendritic cell line XS106 cells and also necrotic cell death called pyroptosis in the cells. The activity was significantly and partially downregulated by silencing of caspase-1 and NLRP3, respectively. BMMs from wild-type and NLRP3-, ASC- and caspase-1-deficient mice were examined for IL-1β production in response to the mycoplasma. Live cells of M. salivarium almost completely lost the activity to induce IL-1β production by macrophages derived from ASC- and caspase-1-deficient mice. In addition, the activity toward BMMs from NLRP3-deficient mice was significantly but not completely attenuated. These results suggest that live cells of M. salivarium are able to activate several types of inflammasome, including the NLRP3 inflammasome, to produce IL-1β. Taken together, the results of this study suggests that M. salivarium plays an etiological role in periodontal diseases through induction of inflammatory IL-1β production by dendritic cells and macrophages that have infiltrated inflamed gingival connective tissue.
Hokkaido University(北海道大学). 博士(歯学)

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