Abstract / Description of output
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 (NFkappaB) regulates expression of many pro-inflammatory mediators. We have assessed the effect of topical administration of NFkappaB decoys in a bleomycin model of acute lung inflammation. Using fluorescein-labelled decoy oligonucleotides (ODN) (80 microg/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 microg/mouse did not increase nuclear transfection significantly. We determined the effect of cytoplasmic NFkappaB decoys on bleomycin-induced inflammation. We transfected mice with 'naked' decoy and scrambled ODN (500 microg) 1 h before intratracheal administration of bleomycin. We measured IL6 secretion in BALF and lung homogenates and total and differential cell counts in BALF 5 days after bleomycin administration. We did not detect a difference between NFkappaB decoy and scrambled ODN-treated animals in any of the parameters tested. We suggest that access of ODN to the nucleus of airway epithelial cells is a key problem, limiting the efficacy of such decoy strategies, as well as attempts at gene repair.
Original language | English |
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Pages (from-to) | 1109-15 |
Number of pages | 7 |
Journal | Gene Therapy |
Volume | 9 |
Issue number | 16 |
DOIs | |
Publication status | Published - Aug 2002 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Bleomycin
- Bronchoalveolar Lavage Fluid
- Cell Nucleus
- Cytoplasm
- Female
- Genetic Therapy
- Interleukin-6
- Lung
- Mice
- Mice, Inbred C57BL
- Molecular Mimicry
- NF-kappa B
- Oligonucleotides
- Pneumonia
- Tissue Distribution
- Transfection