Modulation of miRNA-155 alters manganese nanoparticle-induced inflammatory response

被引:15
作者
Grogg, Matthew W. [1 ]
Braydich-Stolle, Laura K. [1 ]
Maurer-Gardner, Elizabeth I. [1 ]
Hill, Natasha T. [2 ]
Sakaram, Suraj [2 ]
Kadakia, Madhavi P. [2 ]
Hussain, Saber M. [1 ]
机构
[1] AFRL, Bioeffects Div, Mol Bioeffects Branch, Airman Syst Directorate, 711 HPW RHDJ, Dayton, OH 45433 USA
[2] Wright State Univ, Boonshoft Sch Med, Dept Biochem & Mol Biol, Dayton, OH 45435 USA
关键词
IN-VITRO EXPOSURE; MAGNETIC NANOPARTICLES; MICRORNA EXPRESSION; NONCODING RNAS; IMMUNE; CELLS; BRAIN; TRANSLOCATION; SIGNATURES; MECHANISM;
D O I
10.1039/c6tx00208k
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Regulation of gene expression by non-coding RNAs, such as microRNAs (miRNAs), is increasingly being examined in a variety of disciplines. Here we evaluated changes in miRNA expression following metallic nanoparticle (NP) exposure in a mouse neuronal co-culture model. Exposure to manganese (Mn) NPs resulted in oxidative stress, inflammation, and toxicity. Next-generation sequencing (NGS) following an 8 h exposure to Mn NPs (low and high doses) revealed several miRNA candidates that modulate NP induced responses. The lead candidate identified was miR-155, which showed a dose dependent decrease in expression upon Mn exposure. Introduction of a miR-155 mimic into the co-culture to restore miR-155 expression completely abrogated the Mn NP-induced gene and protein expression of inflammatory markers TNF-alpha and IL-6. Taken together, this study is the first report where global NP-induced miRNA expression changes were used to identify and then modulate negative impacts of metallic NP exposure in a neuronal model. These findings demonstrate that unique miRNA expression profiles provide novel targets for manipulating gene and protein expression, and therefore provide the potential of modifying cellular responses to NP exposure.
引用
收藏
页码:1733 / 1743
页数:11
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