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2632873 
Journal Article 
Comparison of non-crystalline silica nanoparticles in IL-1 beta release from macrophages 
Sandberg, WJ; Lag, M; Holme, JA; Friede, B; Gualtieri, M; Kruszewski, M; Schwarze, PerE; Skuland, T; Refsnes, M 
2012 
No 
Particle and Fibre Toxicology
EISSN: 1743-8977 
9 
22882971 
WOS:000308668300001 
Background: Respirable crystalline silica (silicon dioxide; SiO2, quartz) particles are known to induce chronic inflammation and lung disease upon long-term inhalation, whereas non-crystalline (amorphous) SiO2 particles in the submicrometre range are regarded as less harmful. Several reports have demonstrated that crystalline, but also non-crystalline silica particles induce IL-1 beta release from macrophages via the NALP3-inflammasome complex (caspase-1, ASC and NALP3) in the presence of lipopolysaccharide (LPS) from bacteria. Our aim was to study the potential of different non-crystalline SiO2 particles from the nano- to submicro-sized range to activate IL-1 beta responses in LPS-primed RAW264.7 macrophages and primary rat lung macrophages. The role of the NALP3-inflammasome and upstream mechanisms was further explored in RAW264.7 cells.



Results: In the present study, we have shown that 6 h exposure to non-crystalline SiO2 particles in nano- (SiNPs, 5-20 nm, 50 nm) and submicro-sizes induced strong IL-1 beta responses in LPS-primed mouse macrophages (RAW264.7) and primary rat lung macrophages. The primary lung macrophages were more sensitive to Si-exposure than the RAW-macrophages, and responded more strongly. In the lung macrophages, crystalline silica (MinUsil 5) induced IL-1 beta release more potently than the non-crystalline Si50 and Si500, when adjusted to surface area. This difference was much less pronounced versus fumed SiNPs. The caspase-1 inhibitor zYVAD and RNA silencing of the NALP3 receptor reduced the particle-induced IL-1 beta release in the RAW264.7 macrophages. Furthermore, inhibitors of phagocytosis, endosomal acidification, and cathepsin B activity reduced the IL-1 beta responses to the different particles to a similar extent.



Conclusions: In conclusion, non-crystalline silica particles in the nano- and submicro-size ranges seemed to induce IL-1 beta release from LPS-primed RAW264.7 macrophages via similar mechanisms as crystalline silica, involving particle uptake, phagosomal leakage and activation of the NALP3 inflammasome. Notably, rat primary lung macrophages were more sensitive with respect to silica-induced IL-1 beta release. The differential response patterns obtained suggest that silica-induced IL-1 beta responses not only depend on the particle surface area, but on factors and/or mechanisms such as particle reactivity or particle uptake. These findings may suggest that bacterial infection via LPS may augment acute inflammatory effects of non-crystalline as well as crystalline silica particles. 
Non-crystalline and crystalline silica particles; Particle size; Macrophages; Inflammation; IL-1 beta; NALP3 inflammasome; Particle uptake; Phagosomal destabilization