Abstract
Previous work has demonstrated that precipitated (NM-200) and pyrogenic (NM-203) Amorphous Silica Nanoparticles (ASNPs) elicit the inflammatory activation of murine macrophages, with more pronounced effects observed with NM-203. Here, we compare the effects of low doses of NM-200 and NM-203 on human macrophage-like THP-1 cells, assessing how the pre-exposure to these nanomaterials affects the cell response to lipopolysaccharide (LPS). Cell viability was affected by NM-203, but not by NM-200, and only in the presence of LPS. While NM-203 stimulated mTORC1, neither ASNPs activated NFκB or the transcription of its target genes PTGS2 and IL1B. NM-200 and NM-203 caused a block of the autophagic flux and inhibited the LPS-dependent increase of Glutamine Synthetase (GS) expression. Both ASNPs suppressed the activation of caspase-1, delaying the LPS-dependent secretion of IL-1β. Thus, ASNPs modulate several important pathways in human macrophages, altering their response to LPS. NM-203 had larger effects on autophagy, mTORC1 activity and GS expression than NM-200, confirming the higher biological activity of pyrogenic ASNPs when compared with precipitated ASNPs.
Highlights
As the additive E551, Food-grade Amorphous Silica Nanoparticles (ASNP) are among the most widely used nanomaterials in the food industry
To ascertain if pyrogenic and precipitated ASNPs alter the inflammatory response to Pathogen Associated Molecular Patterns (PAMPs), we investigate here the effects of a pre-incubation with NM-200 or NM-203 on several parameters associated with the LPS-mediated activation of human THP-1-macrophages
The results of the present study indicate that, in THP-1 macrophages: (a) ASNPs block autophagy, activate the mTORC1 complex and hinder caspase-1 activation; (b) ASNPs mimic some effects of LPS while impairing Glutamine Synthetase (GS) induction and IL-1β secretion promoted by the endotoxin; (c) pyrogenic ASNPs are distinctly more active than precipitated ASNPs, confirming that, for regulatory purposes, the two materials should not be considered the same
Summary
As the additive E551, Food-grade Amorphous Silica Nanoparticles (ASNP) are among the most widely used nanomaterials in the food industry. They are not engineered to be on the nanoscale, but the traditional production processes result in the synthesis of primary nanoparticles which can variably agglomerate or aggregate depending on the conditions of production and use. The evaluation suffered from significant limitations (in the toxicological database, as well as in the physicochemical characterization of the materials employed in the in vivo studies [1]) and was carried out before the methodology for the nano-specific risk assessment became available [2]. An assessment of E551, addressing the nanoscale nature of the material, highlighted that more insight into the health risk of AS in food was warranted [8]
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