title: SiO2and TiO2nanoparticles synergistically trigger macrophage inflammatory responses.
abstract: Silicon dioxide (SiO2) nanoparticles (NPs) and titanium dioxide (TiO2) NPs are the most widely used inorganic nanomaterials. Although the individual toxicities of SiO2and TiO2NPs have been extensively studied, the combined toxicity of these NPs is much less understood. In this study, we observed unexpected and drastic activation of the caspase-1 inflammasome and production of IL-1β in mouse bone marrow-derived macrophages stimulated simultaneously with SiO2and TiO2NPs at concentrations at which these NPs individually do not cause macrophage activation. Consistent with this, marked lung inflammation was observed in mice treated intratracheally with both SiO2and TiO2NPs. In macrophages, SiO2NPs localized in lysosomes and TiO2NPs did not; while only TiO2NPs produced ROS, suggesting that these NPs induce distinct cellular damage leading to caspase-1 inflammasome activation. Intriguingly, dynamic light scattering measurements revealed that, although individual SiO2and TiO2NPs immediately aggregated to be micrometer size, the mixture of these NPs formed a stable and relatively monodisperse complex with a size of ~250 nm in the presence of divalent cations. Taken together, these results suggest that SiO2and TiO2NPs synergistically induce macrophage inflammatory responses and subsequent lung inflammation. Thus, we propose that it is important to assess the synergistic toxicity of various combinations of nanomaterials.
authors.affiliation: Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Tsugita
authors.affiliation: Department of Materials Processing, Graduate School of Engineering, Tohoku University, Sendai, 980-8579, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Morimoto
authors.affiliation: Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan. mnakayama@fris.tohoku.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D058847:Inflammasomes / Q000276:immunology; D007249:Inflammation; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology; D012822:Silicon Dioxide / Q000493:pharmacokinetics / Q000633:toxicity*; D013499:Surface Properties; D014025:Titanium / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium
keywords: IL-1β; Inflammation; Macrophage; Nanoparticle; SiO2; TiO2