Local administration of transcription factor decoy oligonucleotides to nuclear factor-κB prevents carrageenin-induced inflammation in rat hind paw

D’Acquisto, Fulvio; Ialenti, Armando; Ianaro, Angela; Vaio, R Di; Carnuccio, Rosa

doi:10.1038/sj.gt.3301295

Cited by 58 publications

(28 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

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

et al. 2002

View full text Add to dashboard Cite

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

show abstract

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

View full text Add to dashboard Cite

show abstract

“…On the other hand, the NF-κB targeting strategy includes: (a) blocking the DNA binding of NF-κB using decoy oligodeoxynucleotides (ODNs) [28]; (b) blocking the transactivation of NF-κB using glucocorticoids [93]; or (c) interfering with NF-κB mRNA using NF-κB antisense oligonucleotide (ASO) [43].…”

Section: Nf-κb Inhibition: Strategy For Cancer Therapymentioning

confidence: 99%

NF‐κB as a potential molecular target for cancer therapy

et al. 2007

View full text Add to dashboard Cite

Abstract. Nuclear factor κB (NF-κB), a transcription factor, plays an important role in carcinogenesis as well as in the regulation of immune and inflammatory responses. NF-κB induces the expression of diverse target genes that promote cell proliferation, regulate apoptosis, facilitate angiogenesis and stimulate invasion and metastasis. Furthermore, many cancer cells show aberrant or constitutive NF-κB activation which mediates resistance to chemo-and radio-therapy. Therefore, the inhibition of NF-κB activation and its signaling pathway offers a potential cancer therapy strategy. In addition, recent studies have shown that NF-κB can also play a tumor suppressor role in certain settings. In this review, we focus on the role of NF-κB in carcinogenesis and the therapeutic potential of targeting NF-κB in cancer therapy.Keywords: NF-κB, NF-κB inhibitor, carcinogenesis, cancer therapy Structure, function and regulation of NF-κBNuclear factor-κB (NF-κB) was first identified in 1986 as a transcription factor that binds to a 10 bp DNA element in kappa immunoglobulin light-chain enhancer in B cells [128]. The mammalian NF-κB family consists of 5 members: NF-κB1 (p50/p105), NF-κB2 (p52/p100), c-Rel, RelA (p65) and RelB (Fig. 1). RelA, c-Rel and RelB are synthesized in their mature forms and contain a transactivation domain that interacts with the transcriptional apparatus. On the other hand, NF-κB1 (p50/p105) and NF-κB2 (p52/p100) are synthesized in precursor forms (p100 and p105) which contain C-terminal ankyrin repeats that are proteolysed by the proteasome resulting in the production of mature proteins (p50 and p52). Both p50 and p52 contain a DNA binding domain but lack a transactivation domain. NF-κB proteins exist in unstimulated cells as homo-or heterodimers bound to IκB proteins. Whereas RelB forms only heterodimers, all the other proteins can form both homo-and heterodimers. NF-κB proteins are characterized by the presence of a highly conserved 300 amino acid Rel homology domain that is located toward the N terminus of the protein, and which is responsible for DNA binding, dimerization, and interaction with specific inhibitory factors known as IκB proteins [7,36].

show abstract

“…One mechanism is the use of a transcription factor decoy (TFD) peptide, called double-stranded oligodeoxynucleotide (ODN), that binds the same complementary region of specific DNA sites, competitively inhibiting NF-B binding. 207 Other examples of inhibi-…”

Section: Block Binding Of Nf-b To the Dnamentioning

confidence: 99%

Nuclear transcription factor-κB as a target for cancer drug development

2002

View full text Add to dashboard Cite

Nuclear factor kappa B (NF-B) is a family of inducible transcription factors found virtually ubiquitously in all cells. Since its discovery by Sen and Baltimore in 1986, much has been discovered about its mechanisms of activation, its target genes, and its function in a variety of human diseases including those related to inflammation, asthma, atherosclerosis, AIDS, septic shock, arthritis, and cancer. Due to its role in a wide variety of diseases, NF-B has become one of the major targets for drug development. Here, we review our current knowledge of NF-B, the possible mechanisms of its activation, its potential role in cancer, and various strategies being employed to target the NF-B signaling pathway for cancer drug development.

show abstract

Local administration of transcription factor decoy oligonucleotides to nuclear factor-κB prevents carrageenin-induced inflammation in rat hind paw

Cited by 58 publications

References 53 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

NF‐κB as a potential molecular target for cancer therapy

Nuclear transcription factor-κB as a target for cancer drug development

Contact Info

Product

Resources

About