Comparison of non-crystalline silica nanoparticles in IL-1β release from macrophages

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-1β 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-1β responses in lps-primed raw264.7 macrophages and primary rat lung macrophages. the role of the nalp3-inflammasome and up-stream 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-1β 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-1β 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-1β release in the raw264.7 macrophages. furthermore,inhibitors of phagocytosis,endosomal acidification,and cathepsin b activity reduced the il-1β 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-1β 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-1β release. the differential response patterns obtained suggest that silica-induced il-1β 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. © 2012 sandberg et al.; licensee biomed central ltd.