The Effect of Iron Oxide Nanoparticles on the Functionality of Murine Microglia Stimulated with Lipopolysaccharide
Date Issued
2012
Date
2012
Author(s)
Chung, Min-Chun
Abstract
Superparamagnetic iron oxide nanoparticles have been employed as magnetic resonance imaging contrast agents for a variety of diagnostic applications, including the imaging of the central nervous system (CNS). As the central resident immune cells with macrophage-like functions, microglia are the dominant cells responsible for managing foreign materials invading the CNS. The objective of this study was to investigate the potential effect of iron oxide nanoparticles on functional activities of primary murine microglia stimulated with lipopolysaccharide (LPS). The results showed that iron oxide nanoparticles at concentrations < 100 μg of Fe/mL did not cause cytotoxicity. Confocal imaging revealed that iron oxide nanoparticles were rapidly and markedly engulfed by microglia. Iron oxide nanoparticles inhibited the expression of the activation marker ionized calcium-binding adaptor molecule-1 and the phagocytic activity of LPS-stimulated microglia. In addition, iron oxide nanoparticles inhibited secretion of interleukin (IL)-1β and IL-1β converting enzyme (ICE) activity, whereas tumor necrosis factor (TNF)-α secretion and TNF-α converting enzyme (TACE) activity were unaltered. Furthermore, internalized iron oxide nanoparticles were accumulated in lysosomes. Iron oxide nanoparticles also impaired lysosome proteolytic and cathepsin B activity, and increased lysosomal membrane permeability and alkalinization. These results suggest that the iron oxide nanoparticles may inhibit the cathepsin B activity, which subsequently suppress the activation of ICE and the secretion of IL-1β. Collectively, the present study demonstrated that iron oxide nanoparticles markedly attenuated the activation and functional activities of LPS-stimulated microglia, suggesting an impaired defense capacity of microglia against gram-negative bacteria.
Subjects
interleukin, iron oxide nanoparticles
lipopolysaccharide
lysosome
microglia
Type
thesis
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