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

被引:14
作者
Fisher, Linda
Samuelsson, Malin
Jiang, Yang
Ramberg, Veronica
Figueroa, Ricardo
Hallberg, Einar
Langel, Ulo
Iverfeldt, Kerstin [1 ]
机构
[1] Stockholm Univ, Dept Neurochem, SE-10691 Stockholm, Sweden
[2] Univ Coll, Sodertorns Hogskola, SE-14189 Huddinge, Sweden
关键词
beta-amyloid; astrocytes; cell-penetrating peptide; inflammation; nuclear factor-kappa B; peptide nucleic acid; TRANSCRIPTION FACTOR DECOY; NECROSIS-FACTOR-ALPHA; ALZHEIMERS-DISEASE; PENETRATING PEPTIDES; ENDOTHELIAL-CELLS; ANTIINFLAMMATORY DRUGS; NUCLEAR-LOCALIZATION; BINDING-FACTOR; IN-VITRO; BETA;
D O I
10.1385/JMN/31:03:209
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:209 / 219
页数:11
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