Mechanism of macrophage injury by amorphous silica nanoparticles

<p>Introduction: Recent advances in nanotechnology have led to the development and use of nanomaterials. Despite concerns about human exposure to nanomaterials in various environments, their safety evaluation remains elusive. Amorphous silica nanoparticles (SiO₂NPs) are a particularly widely used nanomaterial, but our laboratory has previously reported that bare SiO₂NPs with hydroxyl groups (OH-SiO₂NPs) may be more injurious to macrophages in vitro and in vivo than SiO₂NPs modified with amino or carboxyl groups. This study aimed to investigate the mechanism of cytotoxicity by OH-SiO₂NPs in vitro. </p><p>Methods: We exposed the mouse macrophage cell line RAW264.7 to OH-SiO₂NPs and treated it with inhibitors of various programmed cell death pathways to examine the relationship between cytotoxicity and each cell death pathway. In addition, mRNA expression levels of inflammatory chemokines and cytokines were measured by RT-qPCR. </p><p>Results and Discussion: Co-treatment with apoptosis and necroptosis inhibitors improved the cell viability, although sole treatment with apoptosis or necroptosis inhibitor did not. The results with inhibitors of various cell death pathways suggest that apoptosis or necroptosis is partially involved in the mechanism of cell death. Additionally, exposure to SiO₂NPs was found to induce the production of pro-inflammatory cytokines and chemokines by macrophages, however, the relationship between this inflammatory response and cytotoxicity should be further investigated.</p>