Inhibition of cerebral vascular inflammation by brain endothelium-targeted oligodeoxynucleotide complex.
Inhibition of cerebral vascular inflammation by brain endothelium-targeted oligodeoxynucleotide complex.
复制标题
脑内皮靶向寡脱氧核苷酸复合物抑制脑血管炎症。
DOI：
10.1016/j.neuroscience.2016.04.033
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Hao,Jiukuan
中科院分区：
文献类型：
--
作者：
Hu,Jing;Al-Waili,Daniah;Hassan,Aishlin;Fan,Guo-Chang;Xin,Mei;Hao,Jiukuan
The present study generated a novel DNA complex to specifically target endothelial NF-κB to inhibit cerebral vascular inflammation. This DNA complex (GS24-NFκB) contains a DNA decoy which inhibits NF-κB activity, and a DNA aptamer (GS-24), a ligand of transferrin receptor (TfR), which allows for targeted delivery of the DNA decoy into cells. The results indicate that GS24-NFκB was successfully delivered into a murine brain-derived endothelial cell line, bEND5, and inhibited inflammatory responses induced by tumor necrosis factor α (TNF-α) or oxygen-glucose deprivation/re-oxygenation (OGD/R) via down-regulation of the nuclear NF-κB subunit, p65, as well as its downstream inflammatory cytokines, inter-cellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1). The inhibitory effect of the GS24-NFκB was demonstrated by a significant reduction in TNF-α or OGD/R induced monocyte adhesion to the bEND5 cells after GS24-NFκB treatment. Intravenous (i.v.) injection of GS24-‘NFκB (15 mg/kg) was able to inhibit the levels of phoseph-p65 and VCAM-1 in brain endothelial cells in a mouse lipopolysaccharide (LPS)-induced inflammatory modelin vivo. In conclusion, our approach using DNA nanotechnology for DNA decoy delivery could potentially be utilized for inhibition of inflammation in ischemic stroke and other neuro-inflammatory diseases affecting cerebral vasculature.
