Targeting cytokine expression in glial cells by cellular delivery of an NF-κB decoy

• Published in: Journal of molecular neuroscience 2007-03, Vol.31 (3), p.209-219
• Main Authors: Fisher, Linda, Samuelsson, Malin, Jiang, Yang, Ramberg, Veronica, Figueroa, Ricardo, Hallberg, Einar, Langel, Ülo, Iverfeldt, Kerstin
• Format: Article
• Language: English
• Subjects: astrocytes; Biochemistry; biokemi; cell-penetrating peptide; inflammation; Neurochemistry and Neurotoxicology; neurokemi och neurotoxikologi; nuclear factor-κB; peptide nucleic acid; β-amyloid
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1385/JMN:31:03:209

Inhibition of nuclear factor (NF)-kappa B has emerged as an important strategy for design of anti-inflammatory therapies. In neurodegenerative disorders like Alzheimer's disease, inflammatory reactions mediated by glial cells are believed to promote disease progression. Here, we report that uptake of a double-stranded oligonucleotide NF-kappa B decoy in rat primary glial cells is clearly facilitated by noncovalent binding to a cell-penetrating peptide, transportan 10, via a complementary peptide nucleic acid (PNA) sequence. Fluorescently labeled oligonucleotide decoy was detected in the cells within 1 h only when cells were incubated with the decoy in the presence of cell-penetrating peptide. Cellular delivery of the decoy also inhibited effects induced by a neurotoxic fragment of the Alzheimer beta-amyloid peptide in the presence of the inflammatory cytokine interleukin (IL)-1 beta. Pretreatment of the cells with the complex formed by the decoy and the cell-penetrating peptide-PNA resulted in 80% and 50% inhibition of the NF-kappa B binding activity and IL-6 mRNA expression, respectively.