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题名: Interference in Autophagosome Fusion by Rare Earth Nanoparticles Disrupts Autophagic Flux and Regulation of an Interleukin-1 beta Producing Inflammasome
作者: Li, Ruibin1;  Ji, Zhaoxia2;  Qin, Hongqiang3;  Kang, Xuedong4;  Sun, Bingbing1;  Wang, Meiying1;  Chang, Chong Hyun2;  Wang, Xiang2;  Zhang, Haiyuan2;  Zou, Hanfa3;  Nel, Andre E.1, 2;  Xia, Tian1, 2
关键词: THP-1 ;  IL-1 beta ;  carbon nanotubes ;  rare earth oxides ;  autophagy ;  NLRP3 inflammasome ;  silica
刊名: ACS NANO
发表日期: 2014-10-01
DOI: 10.1021/nn505002w
卷: 8, 期:10, 页:10280-10292
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Physical Sciences ;  Technology
类目[WOS]: Chemistry, Multidisciplinary ;  Chemistry, Physical ;  Nanoscience & Nanotechnology ;  Materials Science, Multidisciplinary
研究领域[WOS]: Chemistry ;  Science & Technology - Other Topics ;  Materials Science
英文摘要: Engineered nanomaterials (ENMs) including multiwall carbon nanotubes (MWCNTs) and rare earth oxide (REO) nanoparticles, which are capable of activating the NLRP3 inflammasome and inducing IL-1 beta production, have the potential to cause chronic lung toxicity. Although it is known that lysosome damage is an upstream trigger in initiating this pro-inflammatory response, the same organelle is also an important homeostatic regulator of activated NLRP3 inflammasome complexes, which are engulfed by autophagosomes and then destroyed in lysosomes after fusion. Although a number of ENMs have been shown to induce autophagy, no definitive research has been done on the homeostatic regulation of the NLRP3 inflammasome during autophagic flux. We used a myeloid cell line (THP-1) and bone marrow derived macrophages (BMDM) to compare the role of autophagy in regulating inflammasome activation and IL-1 beta production by MWCNTs and REO nanoparticles. THP-1 cells express a constitutively active autophagy pathway and are also known to mimic NLRP3 activation in pulmonary macrophages. We demonstrate that, while activated NLRP3 complexes could be effectively removed by autophagosome fusion in cells exposed to MWCNTs, REO nanoparticles interfered in autophagosome fusion with lysosomes. This leads to the accumulation of the REO-activated inflammasomes, resulting in robust and sustained IL-1 beta production. The mechanism of REO nanoparticle interference in autophagic flux was clarified by showing that they disrupt lysosomal phosphoprotein function and interfere in the acidification that is necessary for lysosome fusion with autophagosomes. Binding of LaPO4 to the REO nanoparticle surfaces leads to urchin-shaped nanoparticles collecting in the lysosomes. All considered, these data demonstrate that in contradistinction to autophagy induction by some ENMs, specific materials such as REOs interfere in autophagic flux, thereby disrupting homeostatic regulation of activated NLRP3 complexes.
关键词[WOS]: WALLED CARBON NANOTUBES ;  CELL-DEATH ;  LYSOSOME IMPAIRMENT ;  GOLD NANOPARTICLES ;  OXIDE NANOCRYSTALS ;  NLRP3 INFLAMMASOME ;  CANCER-CELLS ;  NANOMATERIALS ;  ACCUMULATION ;  TOXICITY
语种: 英语
WOS记录号: WOS:000343952600063
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/145608
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Univ Calif Los Angeles, Dept Med, Div NanoMed, Los Angeles, CA 90095 USA
2.Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA
3.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Natl Chromatog R&A Ctr, Dalian 116023, Peoples R China
4.Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA

Recommended Citation:
Li, Ruibin,Ji, Zhaoxia,Qin, Hongqiang,et al. Interference in Autophagosome Fusion by Rare Earth Nanoparticles Disrupts Autophagic Flux and Regulation of an Interleukin-1 beta Producing Inflammasome[J]. ACS NANO,2014,8(10):10280-10292.
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