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Bronchial epithelium repair by Esculentin-1a-derived antimicrobial peptides: involvement of metalloproteinase-9 and interleukin-8, and evaluation of peptides' immunogenicity.

Authors :
Cappiello, Floriana
Ranieri, Danilo
Carnicelli, Veronica
Casciaro, Bruno
Chen, Han-Tang
Ferrera, Loretta
Di, Y. Peter
Mangoni, Maria Luisa
Source :
Scientific Reports. 12/12/2019, Vol. 9 Issue 1, p1-13. 13p.
Publication Year :
2019

Abstract

The airway epithelium is seriously damaged upon pulmonary Pseudomonas aeruginosa infection, especially in cystic fibrosis (CF) sufferers. Therefore, the discovery of novel anti-infective agents accelerating healing of infected injured tissues is crucial. The antipseudomonal peptides esculentin-1a(1–21)NH2 and its diastereomer Esc(1–21)-1c (Esc peptides) hold promise in this respect. In fact, they stimulate airway epithelial wound repair, but no mechanistic insights are available. Here we demonstrated that this process occurs through promotion of cell migration by an indirect activation of epidermal growth factor receptor mediated by metalloproteinases. Furthermore, we showed an increased expression of metalloproteinase 9, at both gene and protein levels, in peptide-treated bronchial epithelial cells with a functional or mutated form of CF transmembrane conductance regulator. In addition, the two peptides counteracted the inhibitory effect of Pseudomonas lipopolysaccharide (mimicking an infection condition) on the wound healing activity of the airway epithelium, and they enhanced the production of interleukin-8 from both types of cells. Finally, no immunogenicity was discovered for Esc peptides, suggesting their potential safety for clinical usage. Besides representing a step forward in understanding the molecular mechanism underlying the peptide-induced wound healing activity, these studies have contributed to highlight Esc peptides as valuable therapeutics with multiple functions. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20452322
Volume :
9
Issue :
1
Database :
Academic Search Index
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
140314126
Full Text :
https://doi.org/10.1038/s41598-019-55426-x