Cystic fibrosis (CF) is characterized by a deep inflammatory process, with production and release of
cytokines and
chemokines, among which
interleukin 8 (IL-8) represents one of the most important. Accordingly, there is a growing interest in developing
therapies against
IL-8, with the aim of reducing the excessive inflammatory response in the airways of CF patients. Since
transcription factor NF-kappaB plays a critical role in
IL-8 expression, the
transcription factor decoy (TFD) strategy might be of interest. TFD is based on biomolecules mimicking the target sites of
transcription factors (TFs) and able to interfere with TF activity when delivered to target cells. Here, we review the inhibitory effects of decoy
oligodeoxyribonucleotides (ODNs) on expression of
IL-8 gene and secretion of
IL-8 by
cystic fibrosis cells infected by Pseudomonas aeruginosa. In addition, the effects of decoy molecules based on
peptide nucleic acids (PNAs) are discussed. In this respect PNA-
DNA-PNA (PDP) chimeras are interesting: (a) unlike PNAs, they can be complexed with
liposomes and
microspheres; (b) unlike
oligodeoxyribonucleotides (ODNs), they are resistant to DNAses, serum and cytoplasmic extracts; (c) unlike PNA/PNA and PNA/
DNA hybrids, they are potent decoy molecules. Interestingly, PDP/PDP
NF-kappaB decoy chimeras inhibit accumulation of pro-inflammatory mRNAs (including IL-8
mRNA) in P. aeruginosa infected IB3-1, cells reproducing the effects of decoy
oligonucleotides. The effects of PDP/PDP chimeras, unlike ODN-based decoys, are observed even in absence of protection with
lipofectamine. Since
IL-8 is pivotal in pro-inflammatory processes affecting
cystic fibrosis, inhibition of its functions might have a clinical relevance.