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dc.contributor.authorRaudales, Jorge Luis Montenegro
dc.contributor.authorYoshimura, Atsutoshi
dc.contributor.authorSm, Ziauddin
dc.contributor.authorKaneko, Takashi
dc.contributor.authorOzaki, Yukio
dc.contributor.authorUkai, Takashi
dc.contributor.authorMiyazaki, Toshihiro
dc.contributor.authorLatz, Eicke
dc.contributor.authorHara, Yoshitaka
dc.identifier.citationPLoS ONE. 2016, 11 (9).nb_NO
dc.description.abstractDental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1β. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1β precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1β, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1β secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1β secretion by ELISA. We found that calculus induced IL-1β secretion in both human PMNs and PBMCs. Calculus also induced IL-1β in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1β induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1β transcription. To analyze the effect of the inorganic structure, we baked calculus at 250°C for 1 h. This baked calculus failed to induce pro-IL-1β transcription. However, it did induce IL-1β secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1β in mouse macrophages, and baked calculus induced IL-1β in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1β secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in the activation of NLRP3 inflammasome.nb_NO
dc.publisherPublic Library of Sciencenb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleDental calculus stimulates interleukin-1β secretion by activating NLRP3 inflammasome in human and mouse phagocytesnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalPLoS ONEnb_NO
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcode© 2016 Montenegro Raudales et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.nb_NO
cristin.unitnameInstitutt for klinisk og molekylær medisin

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal