The effect of surface modification of amorphous silica particles on NLRP3 inflammasome mediated IL-1beta production, ROS production and endosomal rupture.
Although amorphous silica particles (SPs) are widely used in cosmetics, foods and medicinal products, it has gradually become evident that SPs can induce substantial inflammation accompanied by interleukin-1beta (IL-1beta) production. Here, to develop safe forms of SPs, we examined the mechanisms of SP-induced inflammation and the relationship between particle characteristics and biological responses. We compared IL-1beta production levels in THP-1 human macrophage like cells in response to unmodified SP of various diameters (30- to 1000-nm) and demonstrated that unmodified microsized 1000-nm SP (mSP1000) induced higher levels of IL-1beta production than did smaller unmodified SPs. Furthermore, we found that unmodified mSP1000-induced IL-1beta production was depended on the sequence of reactive oxygen species (ROS) production, endosomal rupture, and subsequent activation of pro-inflammatory complex NLRP3 inflammasome. In addition, we compared IL-1beta production levels in THP-1 cells treated with mSP1000s modified with a functional group (-COOH, -NH(2), -SO(3)H, -CHO). Although unmodified and surface-modified mSP1000s were taken up with similar frequencies equally into the THP-1 cells, surface modification of mSP1000 dramatically suppressed IL-1beta production by reducing ROS production. Our results reveal a part of NLRP3 activation pathway and provide basic information that should help to create safe and effective forms of SPs.
Morishige
Tomohiro
T
Laboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yoshioka
Yasuo
Y
Inakura
Hiroshi
H
Tanabe
Aya
A
Yao
Xinglei
X
Narimatsu
Shogo
S
Monobe
Youko
Y
Imazawa
Takayoshi
T
Tsunoda
Shin-ichi
S
Tsutsumi
Yasuo
Y
Mukai
Yohei
Y
Okada
Naoki
N
Nakagawa
Shinsaku
S
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D011992:Endosomes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry* / Q000494:pharmacology*; D013499:Surface Properties / Q000187:drug effects
D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D002401:Cathepsin B; D020170:Caspase 1