title: Porcine brain microvessel endothelial cells show pro-inflammatory response to the size and composition of metallic nanoparticles.
abstract: 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 (15 μg/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.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration , Jefferson, AR , USA .
authors.forename: William J
authors.initials: WJ
authors.lastname: Trickler
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lantz-McPeak
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Robinson
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: William
authors.initials: W
authors.lastname: Slikker
authors.forename: Alexandru S
authors.initials: AS
authors.lastname: Biris
authors.forename: John J
authors.initials: JJ
authors.lastname: Schlager
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
authors.forename: Jyotshna
authors.initials: J
authors.lastname: Kanungo
authors.forename: Carmen
authors.initials: C
authors.lastname: Gonzalez
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D055806:Microvessels / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000276:immunology; D010316:Particle Size; D013499:Surface Properties; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone