| First Author | Hu J | Year | 2016 |
| Journal | Neuroscience | Volume | 329 |
| Pages | 30-42 | PubMed ID | 27132231 |
| Mgi Jnum | J:235972 | Mgi Id | MGI:5804067 |
| Doi | 10.1016/j.neuroscience.2016.04.033 | Citation | Hu J, et al. (2016) Inhibition of cerebral vascular inflammation by brain endothelium-targeted oligodeoxynucleotide complex. Neuroscience 329:30-42 |
| abstractText | The present study generated a novel DNA complex to specifically target endothelial NF-kappaB to inhibit cerebral vascular inflammation. This DNA complex (GS24-NFkappaB) contains a DNA decoy which inhibits NF-kappaB 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-NFkappaB was successfully delivered into a murine brain-derived endothelial cell line, bEND5, and inhibited inflammatory responses induced by tumor necrosis factor alpha (TNF-alpha) or oxygen-glucose deprivation/re-oxygenation (OGD/R) via down-regulation of the nuclear NF-kappaB 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-NFkappaB was demonstrated by a significant reduction in TNF-alpha or OGD/R induced monocyte adhesion to the bEND5 cells after GS24-NFkappaB treatment. Intravenous (i.v.) injection of GS24-'NFkappaB (15mg/kg) was able to inhibit the levels of phoseph-p65 and VCAM-1 in brain endothelial cells in a mouse lipopolysaccharide (LPS)-induced inflammatory model in 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. |
