Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

Suzuki, Jun–ichi; Morishita, Ryuichi; Amano, Jun; Kaneda, Yasufumi; Isobe, Mitsuaki

doi:10.1038/sj.gt.3301316

Cited by 57 publications

(50 citation statements)

References 31 publications

(49 reference statements)

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“…Although small DNA fragments (Ͻ50 bp) have been widely used as decoy and antisense molecules in vivo, [13][14][15]17,18 their biodistribution after topical administration to the lung has not yet been studied. We have shown that both 'naked' and lipid-complexed decoy ODN have similar biodistribution and subcellular localisation in the lung.…”

Section: Discussionmentioning

confidence: 99%

“…NF B decoy oligonucleotides, which resemble consensus binding sites for NF B, and therefore inactivate the transcription factor have been used successfully in several inflammatory disease animal models. [13][14][15] We have previously demonstrated that NF B decoy oligonucleotides (ODN) reduced basal and LPS-stimulated IL-8 secretion in a CF airway epithelial cell line, 16 but their effect in models of pulmonary inflammation in vivo has not yet been investigated. We have, therefore, assessed the effect of NF B decoy ODN administration during the acute phase of bleomycininduced pulmonary inflammation in C57Bl/6 mice in vivo.…”

Section: Nuclear Transfection Significantly We Determined the Effectmentioning

confidence: 99%

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Cytoplasmic deposition of NFκB decoy oligonucleotides is insufficient to inhibit bleomycin-induced pulmonary inflammation

et al. 2002

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Lung inflammation leads to severe tissue destruction and ultimately organ failure in a number of diseases, including cystic fibrosis (CF). The transcription factor nuclear factor kappa B (NF B) regulates expression of many pro-inflammatory mediators. We have assessed the effect of topical administration of NF B decoys in a bleomycin model of acute lung inflammation. Using fluorescein-labelled decoy oligonucleotides (ODN) (80 g/mouse) we have shown that lipid-complexed and 'naked' ODN transfect conducting airway epithelium in a comparable manner (approximately 65% of cells). However, the ODN were detectable in the cytoplasm, but not in the nucleus of transfected cells. An increase of ODN dose to 500 g/mouse did not increase

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Section: Discussionmentioning

confidence: 99%

Section: Nuclear Transfection Significantly We Determined the Effectmentioning

confidence: 99%

Cytoplasmic deposition of NFκB decoy oligonucleotides is insufficient to inhibit bleomycin-induced pulmonary inflammation

et al. 2002

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“…This may be a useful method for the treatment of a wide spectrum of human diseases (cf. Morishita et al, 24 Ono et al, 25 Sharma et al, 26 Suzuki et al, 27 Vos et al 28 ). However, one of the problems with the transcription factor decoy strategy is that the uptake of DNA into mammalian cells is not very efficient, and therefore high concentrations and long incubation times have to be used to obtain significant effects.…”

Section: Introductionmentioning

confidence: 99%

Cellular delivery of a double-stranded oligonucleotide

et al. 2004

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The activation of nuclear factor kB (NFkB) is a key event in immune and inflammatory responses. In this study, a cellpenetrating transport peptide, transportan (TP) or its shorter analogue TP 10, was used to facilitate the cellular uptake of an NFkB decoy. Peptide nucleic acid (PNA) hexamer or nonamer was linked to the transport peptide by a disulfide bond. NFkB decoy oligonucleotide consisted of a doublestranded consensus sequence corresponding to the kB site localized in the IL-6 gene promoter, 5 0 -GGGACTTTCCC-3 0 , with a single-stranded protruding 3 0 -terminal sequence complementary to the PNA sequence was hybridized to the transport peptide-PNA construct. The ability of the transport peptide-PNA-NFkB decoy complex to block the effect of interleukin (IL)-1b-induced NFkB activation and IL-6 gene expression was analyzed by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction in rat Rinm5F insulinoma cells. Preincubation with transport peptide-PNA-NFkB decoy (1 mM, 1 h) blocked IL-1b-induced NFkB-binding activity and significantly reduced the IL-6 mRNA expression. The same concentration of NFkB decoy in the absence of transport peptide-PNA had no effect even after longer incubations. Our results showed that binding of the oligonucleotide NFkB decoy to the nonamer PNA sequence resulted in a stable complex that was efficiently translocated across the plasma membrane.

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“…One of the most effective decoy approaches so far described involves nuclear proteins belonging to the NF-B 1 superfamily (7)(8)(9)(13)(14)(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites

Borgatti¹,

Lampronti²,

Romanelli³

et al. 2003

Journal of Biological Chemistry

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Peptide nucleic acids (PNAs) are DNA-mimicking molecules in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. We determined whether double-stranded molecules based on PNAs and PNA-DNA-PNA (PDP) chimeras could be capable of stable interactions with nuclear proteins belonging to the Sp1 transcription factor family and, therefore, could act as decoy reagents able to inhibit molecular interactions between Sp1 and DNA. Since the structure of PNA/PNA hybrids is very different from that of the DNA/DNA double helix, they could theoretically alter the molecular structure of the double-stranded PNA-DNA-PNA chimeras, perturbing interactions with specific transcription factors. We found that PNA-based hybrids do not inhibit Sp1/DNA interactions. In contrast, hybrid molecules based on PNA-DNA-PNA chimeras are very effective decoy molecules, encouraging further experiments focused on the possible use of these molecules for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDPbased decoy molecules are more resistant than DNA/ DNA hybrids to enzymatic degradation appears to be of great interest. Furthermore, their resistance can even be improved after complexation with cationic liposomes to which PDP/PDP chimeras are able to bind by virtue of their internal DNA structure.In vitro transfection of cis elements that decoy against nuclear factors leads to alteration of gene expression and was recently proposed in molecular medicine as a novel tool for the possible therapy of several disorders (1-12). One of the most effective decoy approaches so far described involves nuclear proteins belonging to the NF-B 1 superfamily (7-9, 13-20).Decoy molecules against NF-B inhibit the expression of NF-B regulated genes (MHC complex genes, IL2 receptor ␣, Igk, IL6, ␦ opioid receptor, preprogalanin, adhesion molecule-1) (20). More recently, dumbell DNA decoy elements against NF-B were demonstrated to be active in inhibiting ex vivo transcription driven by the long terminal repeat (LTR) of human immunodeficiency type-1 virus (HIV-1) (19). In addition to proteins belonging to the NF-B superfamily, decoy molecules for other target transcription factors, such as HNF-1, RFX1, nuclear factor YB, E2F, cAMP-response element, and Sp1, were found to be effective (1-6, 10 -12, 21).As to the molecular targets for the decoy approach, proteins belonging to the Sp1 family are of great interest since these transcription factors are involved in the regulation of the expression of several genes relevant to human pathologies, including those encoding vascular endothelial growth factor, plasminogen-activator inhibitor type-1 (PAI-1), COL1A2, urokinase-type plasminogen activator (uPA), and uPA receptor (3,(21)(22)(23)(24)(25). Sp1 binding sites are also present in the HIV-1 LTR (26). Thus, the development of experimental approaches based on Sp1 decoys to modulate the transcription of Sp1-dependent genes appears to be of great interest (3).Rec...

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Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

Cited by 57 publications

References 31 publications

Cytoplasmic deposition of NFκB decoy oligonucleotides is insufficient to inhibit bleomycin-induced pulmonary inflammation

Cytoplasmic deposition of NFκB decoy oligonucleotides is insufficient to inhibit bleomycin-induced pulmonary inflammation

Cellular delivery of a double-stranded oligonucleotide

Transcription Factor Decoy Molecules Based on a Peptide Nucleic Acid (PNA)-DNA Chimera Mimicking Sp1 Binding Sites

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