Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes

Abstract

Co-stimulation of the immune system to more than one agent concomitantly is very common in real life, and considering the increasing use of engineered nanoparticles and nanomaterials, it is highly relevant to assess the ability of these materials to modulate key innate immune responses, which has not yet been studied in detail. We investigated the immunomodulatory effects of 10 nm and 30 nm iron oxide nanoparticles (IONPs) on primary human monocytes in the presence and absence of Toll-like receptor 4 agonist lipopolysaccharide (LPS). Prior to the cell studies, we characterized the physicochemical properties of the nanoparticles in cell culture medium and ensured that the nanoparticles were free from biological contamination. Cellular uptake of the IONPs in monocytes was assessed using transmission electron microscopy. Using enzyme-linked immunosorbent assay, we found that the IONPs per se did not induce the production of proinflammatory cytokines tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, the IONPs had the ability to suppress LPS-induced nuclear factor kappa B activation and production of proinflammatory cytokines in primary human monocytes in an LPS and a particle dose-dependent manner. Using confocal microscopy and fluorescently labeled LPS, we showed that the effects correlated with impaired LPS internalization by monocytes in the presence of IONPs, which could be partly explained by LPS adsorption onto the nanoparticle surface. Additionally, the results from particle pretreatment experiments indicate that other cellular mechanisms might also play a role in the observed effects, which warrants further studies to elucidate the additional mechanisms underlying the capacity of IONPs to alter the reactivity of monocytes to LPS and to mount an appropriate cellular response.

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

“…Such a negative regulatory effect might be similar to the adsorption and inactivation of LPS that we previously described using the same IONPs in cell culture. 14 In order to examine if the cytokine response in our study was accompanied by ROS production, we measured intracellular ROS in the whole blood samples after 2 and 4 h. The IONPs did not significantly increase ROS compared with the control samples, which is in agreement with previous findings. 30,31 However, our results are in contrast to other studies that show IONP-induced ROS production.…”

“…Particle contamination with endotoxin/LPS or bacterial lipoproteins could potentially be the reason for the cytokine production. However, as previously demonstrated, 14 contamination of the IONPs can be excluded.…”

“…11 Moreover, non-coated and polyacrylic acid-coated IONPs induced IL-1β, IL-8, IL-6, TNF and IL-10 in primary human blood cells 12 and aminopolyvinyl alcohol-coated SPION increased the secretion of IL-1β, IL-4, IL-8, IL-6, MIP-1β and RANTES in whole blood samples. 13 In contrast, we did not observe pro-inflammatory cytokine production by IONPs in primary human monocytes, 14 which might be due to different properties of the IONPs and different cell types used.…”

“…An initial characterization of the IONPs as to their hydrodynamic diameter, zeta potential and chemical composition was done in our previous study 14 and is shown in Table 1. In the present study, we additionally determined the hydrodynamic diameter of the IONPs in PBS as the IONPs were dispersed in PBS before adding to the whole blood samples.…”

Long Exposure to CdS-Dextrin Nanoparticles Induces an Immunomodulatory and Anti-Inflammatory Effect in Rats

“…Several studies show nanomaterials can stimulate or suppress the immunological response, and there is evidence that their immunogenicity depends largely on their physicochemical characteristics; e.g., size, shape, charge, composition, the chemical groups on the surface, coating, and the state of the biological environment [13][14][15][16][17][18]. It is currently a difficult task to predict how the immunological system will respond to a determined nanomaterial and if the response will be the same in a healthy or diseased condition considering possible theranostic uses.…”