Porcine brain microvessel endothelial cells show pro-inflammatory response to the size and composition of metallic nanoparticles
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The purpose of the current studies was to determine if systemic exposure of various metallic nanoparticles differing in size and composition [silver (Ag-NPs, 25, 40 and 80 nm), copper-oxide (Cu-NPs, 40 and 60 nm) or gold (Au-NPs, 3 and 5 nm)] can induce the release of pro-inflammatory mediators that influence the restrictive nature of the blood-brain barrier (BBB) in vitro. Confluent porcine brain microvessel endothelial cells (pBMECs) (8-12 days) were treated with various metallic nanoparticles (15μg/ml). Extracellular concentrations of pro-inflammatory mediators (IL-1β, TNFα and PGE2) were evaluated using ELISA. pBMECs were cultured in standard 12-well Transwell® inserts, and permeability was evaluated by measuring the transport of fluorescein across the pBMEC monolayers. PGE2 release following Cu-NP exposure was significantly increased when compared to the control. Similar results were observed for Ag-NPs but not Au-NPs. The secretion of TNFα and IL-1β was observed for both Cu-NPs and Ag-NPs but not in response to Au-NPs. The post-treatment time profiles of TNFα and IL-1β revealed that the IL-1β response was more persistent. The permeability ratios (exposure/control) were significantly greater following exposure to Cu-NPs or Ag-NPs, compared to Au-NPs. Together, these data suggest that the composition and size of NPs can cause significant pro-inflammatory response that can influence the integrity of the BBB. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.
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Blood-brain barrier; Lipopolysaccharide (LPS); Metallic-colloidal nanoparticles; Neuroinflamation; Neurotoxicity; Porcine brain microvessel endothelial cells copper nanoparticle; fluorescein; gold nanoparticle; interleukin 1beta; prostaglandin E2; silver nanoparticle; tumor necrosis factor alpha; autacoid; interleukin 1beta; metal nanoparticle; prostaglandin E2; tumor necrosis factor alpha; animal cell; blood brain barrier; brain capillary endothelial cell; cell membrane permeability; concentration (parameters); controlled study; cytokine release; enzyme linked immunosorbent assay; experimental pig; in vitro study; nervous system inflammation; nonhuman; particle size; review; animal; chemistry; cytology; drug effects; endothelium cell; immunology; microvasculature; Neurotoxicity Syndromes; particle size; secretion (process); surface property; swine; toxicity; Animals; Blood-Brain Barrier; Dinoprostone; Endothelial Cells; Inflammation Mediators; Interleukin-1beta; Metal Nanoparticles; Microvessels; Neurotoxicity Syndromes; Particle Size; Surface Properties; Swine; Tumor Necrosis Factor-alpha
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