Inhibition of cerebral vascular inflammation by brain endothelium-targeted oligodeoxynucleotide complex

Jing Hu, Daniah Al-Waili, Aishlin Hassan, Guo Chang Fan, Mei Xin, Jiukuan Hao

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)30-42
Number of pages13
JournalNeuroscience
Volume329
DOIs
StatePublished - Aug 4 2016

Keywords

  • Aptamer
  • Endothelial cells
  • Inflammation
  • Lipopolysaccharide
  • NF-κB
  • Oxygen-glucose deprivation

ASJC Scopus subject areas

  • Neuroscience(all)

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