SiO 2 and TiO 2 nanoparticles synergistically trigger macrophage inflammatory responses
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SiO2 and TiO2 nanoparticles synergistically trigger macrophage inflammatory responses Misato Tsugita1, Nobuyuki Morimoto2 and Masafumi Nakayama1*
Abstract Silicon dioxide (SiO2) nanoparticles (NPs) and titanium dioxide (TiO2) NPs are the most widely used inorganic nanomaterials. Although the individual toxicities of SiO2 and TiO2 NPs 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 SiO2 and TiO2 NPs 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 SiO2 and TiO2 NPs. In macrophages, SiO2 NPs localized in lysosomes and TiO2 NPs did not; while only TiO2 NPs 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 SiO2 and TiO2 NPs 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 SiO2 and TiO2 NPs 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. Keywords: SiO2, TiO2, Nanoparticle, Macrophage, IL-1β, Inflammation
Background With the development of nanotechnology, the production and distribution of engineered nanomaterials (ENMs) is rapidly expanding [1, 2]. The most frequently used nanomaterials are inorganic nanoparticles (NPs) such as silicon dioxide (SiO2) and titanium dioxide (TiO2) [2]. Indeed, these NPs are currently used in a wide variety of materials including paints, cosmetics, and pharmaceutical products [3, 4]. Both SiO2 and TiO2 had been considered to be biocompatible; however, numerous recent studies have shown that particle size impacts toxicity [5, 6]. For instance, while micro-sized SiO2 and TiO2 particles rarely cause inflammation, their NPs do [7–9]. Given the current expanding use of ENMs, the assessment of any health risks associated with these materials is the globally important. In this context, the toxicity of individual * Correspondence: [email protected] 1 Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-AobaAoba-ku, Sendai 980-8578, Japan Full list of author information is available at the end of the article
ENMs has been extensively studied; however, the combined toxicity of multiple ENMs has not. Therefore, because it is likely that our bodies are exposed simultaneously to a wide variety type of ENMs, the combined toxicity of multiple ENMs should be extensively addressed. When N
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