Abstract
Because of their low cost and easy production, silica nanoparticles (SiNPs) are widely used in multiple manufacturing applications as anti-caking, densifying and hydrophobic agents. However, this has increased the exposure levels of the general population and has raised concerns about the toxicity of this nanomaterial. SiNPs affect the function of the airway epithelium, but the biochemical pathways targeted by these particles remain largely unknown. Here we investigated the effects of SiNPs on the responses of 16HBE14o- cultured human bronchial epithelial (16HBE) cells to the damage-associated molecular pattern ATP, using fluorometric measurements of intracellular Ca2+ concentration. Upon stimulation with extracellular ATP, these cells displayed a concentration-dependent increase in intracellular Ca2+, which was mediated by release from intracellular stores. SiNPs inhibited the Ca2+ responses to ATP within minutes of application and at low micromolar concentrations, which are significantly faster and more potent than those previously reported for the induction of cellular toxicity and pro-inflammatory responses. SiNPs-induced inhibition is independent from the increase in intracellular Ca2+ they produce, is largely irreversible and occurs via a non-competitive mechanism. These findings suggest that SiNPs reduce the ability of airway epithelial cells to mount ATP-dependent protective responses.
Highlights
ATP is a key messenger of cellular damage, and its detection plays a key role in activating protective mechanisms in neighboring healthy cells
Previous studies have established the implication of ATP-mediated signaling upon exposure to nanomaterials, including silica
These have mainly reported the induction of ATP release upon long-term exposure, from 30–40 min [47,48,49] to several hours [46,68,69]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Human exposure to NPs has increased considerably since the nano-technological revolution Their small dimensions and unique physico-chemical properties facilitate the ability of nanoparticles to cross different barriers and to reach distal organs [8,9,10,11,12]. They can penetrate the plasma membrane and deposit into subcellular structures such as mitochondria, endoplasmic reticulum and lysosomes, thereby posing potential health threats [13,14,15,16,17]. This suggests that SiNPs affect the ability of airway epithelial cells to respond to environmental and endogenous stimuli that require ATP-mediated signaling
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