Fernando T. Andon, Sourav P. Mukherjee, Isabel Gessner, Laura Wortmann, Lisong Xiao, Kjell Hultenby, Anna A. Shvedova, Sanjay Mathur, Bengt Fadeel
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 humanmonocyte-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 secretionwas 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.
Carbon 2017, 113, 243-251.
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