The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles

Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the response of innate immunity cells to natural activators has not been thoroughly investigated. Here, we study the effects of pyrogenic ASNP on the LPS-dependent activation of human macrophages differentiated from peripheral blood monocytes. In macrophages, 24 h of pre-exposure to non-cytotoxic doses of ASNP markedly inhibited the LPS-dependent induction of pro-inflammatory (TNF alpha, IL-6) and anti-inflammatory cytokines (IL-10). The inhibitory effect was associated with the suppression of NF kappa B activation and the increased intracellular sequestration of the TLR4 receptor. The late induction of glutamine synthetase (GS) by LPS was also prevented by pre-exposure to ASNP, while GS silencing did not interfere with cytokine secretion. It is concluded that (i) macrophages exposed to ASNP are less sensitive to LPS-dependent activation and (ii) GS induction by LPS is likely secondary to the stimulation of cytokine secretion. The observed interference with LPS effects may point to a dampening of the acute inflammatory response after exposure to ASNP in humans.

Automated summary

Amorphous silica nanoparticles (ASNP) inhibit the response of human macrophages to natural activators, suppressing the production of pro-inflammatory and anti-inflammatory cytokines. This inhibition is achieved by suppressing NF kappa B activation and increasing the intracellular sequestration of the TLR4 receptor. Induction of glutamine synthetase (GS) may be secondary to cytokine stimulation. These findings suggest a dampening of the acute inflammatory response after exposure to ASNP.