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Selective stimulation of the JAK/ ST AT signaling pathway by silica nanoparticles in human endothelial cells

Siegrist, Stefan and Kettiger, Helene and Fasler-Kan, E. and Huwyler, Jörg. (2017) Selective stimulation of the JAK/ ST AT signaling pathway by silica nanoparticles in human endothelial cells. Toxicology in Vitro, 42. pp. 308-318.

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Official URL: http://edoc.unibas.ch/55245/

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Abstract

Silica nanoparticles (SiNP) are frequently used in pharmaceutical formulations. Intravenously administered, these particles are in close contact with the vascular endothelium. However, preliminary safety assessments of these novel excipients have indicated that SiNP are potentially cytotoxic and can trigger inflammation. In order to elucidate mechanisms of SiNP mediated inflammation, cerebral microvascular endothelial cells and primary umbilical endothelial cells were incubated with SiNP at doses between 10 ng/ml and 250 μg/ml. Two types of 110 nm SiNP with different surface charge were synthesized and characterized. Uptake, cell viability, apoptosis, necrosis, oxidative stress, as well as interferences with both JAK/STAT and NF-κB pathways were studied. SiNP uptake leads to a cell viability decrease and promotes generation of reactive oxygen species (ROS) in a time- and dose-dependent manner. Furthermore, SiNP are able to trigger the activation of the STAT1 pathway. In contrast, no significant activation of STAT3, STAT6 or NF-κB could be detected. Additionally, modulation of the major histocompatibility complex (MHC) class I proteins was observed for cationic SiNP at low doses. Our results show the potential of SiNP to trigger selective activation of inflammatory signaling pathways in endothelial cells and thereby contribute to a better understanding of the toxicological profile of SiNP.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Siegrist, Stefan and Kettiger, Helene
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0887-2333
e-ISSN:1879-3177
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Oct 2017 06:45
Deposited On:20 Oct 2017 06:45

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