期刊
TOXICOLOGY IN VITRO
卷 42, 期 -, 页码 308-318出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2017.05.002
关键词
Nanotoxicology; Silica nanoparticles; Reactive oxygen species; JAK/STAT; MHC class I
类别
资金
- Swiss Center for Applied Human Toxicology (SCAHT)
- NanoReg2 Program (European Union Horizon research) [646221, 15.0200-3]
- Swiss National Science Foundation [31003A_173057]
- Swiss National Science Foundation (SNF) [31003A_173057] Funding Source: Swiss National Science Foundation (SNF)
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 mu g/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-kappa B 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-kappa B 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.
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