期刊
NANOTOXICOLOGY
卷 5, 期 4, 页码 568-582出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/17435390.2010.537791
关键词
Metal nanoparticles; hypoxia inducible factor 1 alpha; matrix metalloproteinases; human monocyte U937; tissue inhibitor of metalloproteinases
资金
- American Lung Association [RG-872-N]
- American Heart Association [086576D]
- Health Effects Institute [4751-RFA-05-2/06-12]
- CTSPGP from University of Louisville [20018, T32-ES011564, ES01443]
- United States Environmental Protection Agency (EPA) [R-8281101]
- [KSEF-1686-RED-11]
Nickel is an important economic commodity, but it can cause skin sensitization and may cause lung diseases such as lung fibrosis, pneumonitis, bronchial asthma and lung cancer. With development of nanotechnology, nano-sized nickel (Nano-Ni) and nano-sized titanium dioxide (Nano-TiO2) particles have been developed and produced for many years with new formulations and surface properties to meet novel demands. Our previous studies have shown that Nano-Ni instilled into rat lungs caused a greater inflammatory response as compared with standard-sized nickel (5 mu m) at equivalent mass concentrations. Nano-Ni caused a persistent high level of inflammation in lungs even at low doses. Recently, several studies have shown that nanoparticles can translocate from the lungs to the circulatory system. To evaluate the potential systemic effects of metal nanoparticles, we compared the effects of Nano-Ni and Nano-TiO2 on matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) gene expression and activity. Our results showed that exposure of human monocyte U937 to Nano-Ni caused dose- and time- dependent increase in MMP-2 and MMP-9 mRNA expression and pro-MMP-2 and pro-MMP-9 activity, but Nano-TiO2 did not. Nano-Ni also caused dose- and time- related increase in tissue inhibitor of metalloproteinases 1 (TIMP-1), but Nano-TiO2 did not. To determine the potential mechanisms involved, we measured the expression of hypoxia inducible factor 1 alpha (HIF-1 alpha) in U937 cells exposed to Nano-Ni and Nano-TiO2. Our results showed that exposure to Nano-Ni caused HIF-1 alpha accumulation in the nucleus. Furthermore, pre-treatment of U937 cells with heat shock protein 90 (Hsp90) inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), prior to exposure to Nano-Ni significantly abolished Nano-Ni-induced MMP-2 and MMP-9 mRNA upregulation and increased pro-MMP-2 and pro-MMP-9 activity. Our results suggest that HIF-1 alpha accumulation may be involved in the increased MMP-2 and MMP-9 production in U937 cells exposed to Nano-Ni.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据