Targeting cytokine expression in glial cells by cellular delivery of an NFκB decoy
2007 (English)In: Journal of Molecular Neuroscience, ISSN 0895-8696, E-ISSN 1559-1166, Vol. 31, no 3, 209-219 p.Article in journal (Refereed) Published
Inhibition of nuclear factor (NF)-κB 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-κB 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 β amyloid peptide in the presence of the inflammatory cytokine interleukin (IL) 1β. 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-κB binding activity and IL-6 mRNA expression, respectively.
Place, publisher, year, edition, pages
2007. Vol. 31, no 3, 209-219 p.
β-amyloid, astrocytes, cell-penetrating peptide, inflammation, nuclear factor-κB, peptide nucleic acid
Research subject Biochemistry; Neurochemistry and Neurotoxicology
IdentifiersURN: urn:nbn:se:su:diva-25921DOI: 10.1385/JMN:31:03:209ISI: 000246588800003OAI: oai:DiVA.org:su-25921DiVA: diva2:200802