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2016 ; 11
(9
): e0162865
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gab.com Text
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English Wikipedia
Dental Calculus Stimulates Interleukin-1? Secretion by Activating NLRP3
Inflammasome in Human and Mouse Phagocytes
#MMPMID27632566
Montenegro Raudales JL
; Yoshimura A
; Sm Z
; Kaneko T
; Ozaki Y
; Ukai T
; Miyazaki T
; Latz E
; Hara Y
PLoS One
2016[]; 11
(9
): e0162865
PMID27632566
show ga
Dental 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-1?. Studies have shown that cellular uptake
of crystalline particles may trigger NLRP3 inflammasome activation, leading to
the cleavage of the IL-1? precursor to its mature form. Phagocytosis of dental
calculus in the periodontal pocket may therefore lead to the secretion of IL-1?,
promoting inflammatory responses in periodontal tissues. However, the capacity of
dental calculus to induce IL-1? 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-1? secretion by ELISA. We found that
calculus induced IL-1? secretion in both human PMNs and PBMCs. Calculus also
induced IL-1? in macrophages from wild-type mice, but not in macrophages from
NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1?
induction was inhibited by polymyxin B, suggesting that LPS is one of the
components of calculus that induces pro-IL-1? 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-1? transcription. However, it did induce IL-1?
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-1? in mouse macrophages, and baked
calculus induced IL-1? in lipid A-primed human PMNs and PBMCs. These results
indicate that dental calculus stimulates IL-1? secretion via NLRP3 inflammasome
in human and mouse phagocytes, and that the crystalline structure has a partial
role in the activation of NLRP3 inflammasome.