Authors: William J. Trickler, Susan M. Lantz, Bonnie L. Robinson, Glenn D. Newport, Paul C. Howard, Alexandru S. Biris, Merle G. Paule, William Slikker, Jr., John J. Schlager, Saber M. Hussain, and Syed F. Ali
Publication: Drug Metabolism Reviews, Volume 46, Issue 2
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.