学位論文 Activation of NLRP3 inflammasome in dendritic cells and macrophages by Mycoplasma salivarium

杉山, 正博

2015-03-25
内容記述
The proinflammatory cytokine IL-1β plays crucial roles in the pathogenesis ofperiodontal 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 proteinand procaspase-1, called an the inflammasome. Mycoplasma salivarium, human oralmicrobial flora, preferentially inhabits the gingival sulcus and is considered to play anetiological role in periodontal diseases. As a first step to clarify the etiological role ofthe organism in periodontal diseases, this study was designed to clarify whether itinduces production of IL-1β by innate immune cells such as dendritic cells ormacrophages by using M. pneumoniae, which is known to induce production of IL-1βby human macrophages, as a positive control.It was found that both live and heat-killed cells of M. salivarium induced productionof IL-1β by the murine dendritic cell line XS106 cells and also necrotic cell death calledpyroptosis in the cells. The activity was significantly and partially downregulated bysilencing 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 tothe mycoplasma. Live cells of M. salivarium almost completely lost the activity toinduce IL-1β production by macrophages derived from ASC- and caspase-1-deficientmice. In addition, the activity toward BMMs from NLRP3-deficient mice wassignificantly but not completely attenuated. These results suggest that live cells of M.salivarium are able to activate several types of inflammasome, including the NLRP3inflammasome, to produce IL-1β.Taken together, the results of this study suggests that M. salivarium plays anetiological role in periodontal diseases through induction of inflammatory IL-1βproduction by dendritic cells and macrophages that have infiltrated inflamed gingivalconnective tissue.
Hokkaido University(北海道大学). 博士(歯学)
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https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/60276/1/Masahiro_Sugiyama.pdf

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