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

Abstract

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 (TNFα, IL-6) and anti-inflammatory cytokines (IL-10). The inhibitory effect was associated with the suppression of NFκB 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.

Identification of the potential cytokines involved in LPS induced acute lung injury in mouse

“…Apart from genes above mentioned, IL-6, a traditional proin ammatory mediator, was ubiquitously adopted as an in vitro in ammatory biomarker because it is a downstream molecule of TLR4/NF-kappaB induced by LPS. IL-6 is overexpressed in ALI through the interaction between LPS and TLR4, and followed by activation and phosphorylation of NF-kappaB, eventually leading to the secretion of IL-6 in supernatant, the whole process is TLR4 dependent 23 . In this way, IL-6 was adopted as the indicator of in ammation in in vivo experiment as well as TNF-a.…”

Colon-available mango (poly)phenols exhibit mitigating effects on the intestinal barrier function in human intestinal cell monolayers under inflammatory conditions

“…Total RNA isolation and reverse transcription were performed as described in 26 . The quality of RNA was monitored and considered optimal only if the ratio of the absorbance values measured at 260/280 nm was between 1.80 and 2.00.…”

Amorphous silica nanoparticles and the human gut microbiota: a relationship with multiple implications

“…Most contributions obtained in murine models indicate that ASNP can exert an activating effect on macrophages [ 58 – 61 ], with pyrogenic ASNP apparently more effective than their precipitated counterparts upon acute exposure [ 59 ]. However, in human macrophages, when used at low, non-toxic doses, ASNP, rather than activate macrophages, can rather modulate their response to natural PAMPs, such as LPS, leading to the intracellular sequestration of membrane receptors and, thus, interfering with cytokine secretion and activation-associated metabolic changes [ 62 , 63 ].…”