An antisense peptide nucleic acid against Pseudomonas aeruginosa inhibiting bacterial-induced inflammatory responses in the cystic fibrosis IB3-1 cellular model system.

Abstract

Discovery of novel antimicrobial agents against Pseudomonas aeruginosa able to inhibit bacterial growth as well as the resulting inflammatory response is a key goal in cystic fibrosis research. We report in this paper that a peptide nucleic acid (PNA3969) targeting the translation initiation region of the essential acpP gene of P. aeruginosa, and previously shown to inhibit bacterial growth, concomitantly also strongly inhibits induced up-regulation of the pro-inflammatory markers IL-8, IL-6, G-CSF, IFN-γ, IP-10, MCP-1 and TNF-α in IB3-1 cystic fibrosis cells infected by P. aeruginosa PAO1. Remarkably, no effect on PAO1 induction of VEGF, GM-CSF and IL-17 was observed. Analogous experiments using a two base mis-match control PNA did not show such inhibition. Furthermore, no significant effects of the PNAs were seen on cell growth, apoptosis or secretome profile in uninfected IB3-1 cells (with the exception of a PNA-mediated up-regulation of PDGF, IL-17 and GM-CSF). Thus, we conclude that in cell culture an antimicrobial PNA against P. aeruginosa can inhibit the expression of pro-inflammatory cytokines otherwise induced by the infection. In particular, the effects of PNA-3969 on IL-8 gene expression are significant considering the key role of this protein in the cystic fibrosis inflammatory process exacerbated by P. aeruginosa infection.

• Authors: Giulia Montagner, Valentino Bezzerri, Giulio Cabrini, Enrica Fabbri, Monica Borgatti, Ilaria Lampronti, Alessia Finotti, Peter E Nielsen, Roberto Gambari
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 99 Pg. 492-498 (Jun 2017) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 28167114 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Interleukin-8
• Oligonucleotides, Antisense
• Peptide Nucleic Acids

Topics

• Apoptosis (genetics)
• Cell Line
• Cell Proliferation (genetics)
• Cystic Fibrosis (pathology)
• Humans
• Inflammation (complications, genetics, microbiology)
• Interleukin-8 (genetics)
• Oligonucleotides, Antisense (genetics)
• Peptide Nucleic Acids (genetics)
• Pseudomonas aeruginosa (genetics, growth & development, physiology)
• Up-Regulation (genetics)