Hollow carbon spheres trigger inflammasome-dependent IL-1β secretion in macrophages
Public Domain
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2017/03/01
Details
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Personal Author:Andón FT ; Fadeel B ; Gessner I ; Hultenby K ; Mathur S ; Mukherjee SP ; Shvedova AA ; Wortmann L ; Xiao L
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Description:It is disputed whether inflammasome activation leading to secretion of pro-inflammatory interleukin (IL)-1β in macrophages transpires independently of cell death or whether the two processes are linked. Here, we synthesized hollow carbon spheres (HCS) and investigated their effects on primary human monocyte-derived macrophages (HMDM); short (500 nm) non-functionalized single-walled carbon nanotubes (SWCNT) were included for comparison. HCS (250 nm) were readily taken up by HMDM and induced ROS production, but did not trigger a loss of cell viability. However, a dose- and time-dependent release of IL-1β was detected in lipopolysaccharide (LPS)-primed macrophages upon exposure to HCS, while SWCNT-induced secretion of IL-1β was less pronounced. HCS-triggered IL-1β secretion was cathepsin B- and caspase-1-dependent, and was accompanied by a reduction in intracellular K+. Furthermore, cytokine secretion was reduced following treatment with the antioxidant, N-acetylcysteine, and cytochalasin D, an inhibitor of actin polymerization. HCS also triggered IL-1β release in LPS-primed THP.1 cells, but not in THP.1 cells with silencing of ASC, NLRP3, or caspase-1 expression, providing evidence that IL-1β was elicited through NLRP3 inflammasome activation. These studies shed light on the effects of HCS on primary macrophages, and show that spherical carbon-based nanoparticles are potent inflammasome activators. [Description provided by NIOSH]
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ISSN:0008-6223
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Pages in Document:243-251
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Volume:113
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NIOSHTIC Number:nn:20049014
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Citation:Carbon 2017 Mar; 113:243-251
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Contact Point Address:Bengt Fadeel, Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm; 17177, Sweden
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Email:Bengt.Fadeel@ki.se
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Federal Fiscal Year:2017
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Peer Reviewed:True
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Source Full Name:Carbon
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Main Document Checksum:urn:sha-512:ddfd9b00c446f0e66d14cfb7286d2f2eaa2d72cbc4612a76729906c5ba26c3fc0b1c25ae13435aca928b394be3339e4d84ab9ea863ca7c7d20e6fd624159fa96
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