Cytokine production by co-cultures exposed to monodisperse amorphous silica nanoparticles: The role of size and surface area

The aim of this study was to test the influence of nanoparticle size and surface area (SA) on cytokine secretion by co-cultures of pulmonary epithelial cells (A549), macrophages (differentiated THP-1 cells) and endothelium cells (EA.hy926) in a two-compartment system. We used monodisperse amorphous silica nanoparticles (2, 16, 60 and 104 nm) at concentrations of 5 μg/cm2 cell culture SA or 10 cm2 particle SA/cm2. A549 and THP-1 cells were exposed to nanoparticles for 24 h, in the presence of EA.hy926 cells cultured in an insert introduced above the bi-culture after 12 h. Supernatants from both compartments were recovered and TNF-α, IL-6, IL-8 and MIP-1α were measured. Significant secretion of all cytokines was observed for the 2 nm particles at both concentrations and in both compartments. Larger particles of 60 nm induced significant cytokine secretion at the dose of 10 cm2 particle SA/cm2. The use of multiple cellular types showed that cytokine secretion in single cell cultures is amplified or mitigated in co-cultures. The release of pro-inflammatory mediators by endothelial cells not directly exposed to nanoparticles indicates a possible endothelium activation after inhalation of silica particles. This work shows the role of size and SA in cellular response to amorphous nanosilica.

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► Size and surface area of silica nanoparticles have influence on cytokine secretion.
► The smallest nanoparticles induce the most pronounced response in cytokine secretion.
► Exposure of co-cultured epithelial cells with macrophages activates endothelial cells.