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Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity

Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity


Title: Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
Author: Myszor, Iwona T.
Parveen, Zahida
Ottosson, Håkan
Bergman, Peter
Agerberth, Birgitta
Strömberg, Roger
Gudmundsson, Gudmundur H   orcid.org/0000-0001-5793-0565
Date: 2019-05-08
Language: English
Scope: 7114
University/Institute: Háskóli Íslands
University of Iceland
School: Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Department: Lífvísindasetur (HÍ)
Biomedical Center (UI)
Series: Scientific Reports;9(1)
ISSN: 2045-2322
DOI: 10.1038/s41598-019-43350-z
Subject: Antimicrobial Peptide LL 37; Cell signalling; Innate immunity; Frumulíffræði; Ónæmiserfðafræði
URI: https://hdl.handle.net/20.500.11815/1995

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Citation:

Myszor, I.T., Parveen, Z., Ottosson, H. et al. Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity. Sci Rep 9, 7114 (2019). https://doi.org/10.1038/s41598-019-43350-z

Abstract:

Aroylated phenylenediamines (APDs) are novel inducers of innate immunity enhancing cathelicidin gene expression in human bronchial epithelial cell lines. Here we present two newly developed APDs and aimed at defining the response and signaling pathways for these compounds with reference to innate immunity and antimicrobial peptide (AMP) expression. Induction was initially defined with respect to dose and time and compared with the APD Entinostat (MS-275). The induction applies to several innate immunity effectors, indicating that APDs trigger a broad spectrum of antimicrobial responses. The bactericidal effect was shown in an infection model against Pseudomonas aeruginosa by estimating bacteria entering cells. Treatment with a selected APD counteracted Pseudomonas mediated disruption of epithelial integrity. This double action by inducing AMPs and enhancing epithelial integrity for one APD compound is unique and taken as a positive indication for host directed therapy (HDT). The APD effects are mediated through Signal transducer and activator of transcription 3 (STAT3) activation. Utilization of induced innate immunity to fight infections can reduce antibiotic usage, might be effective against multidrug resistant bacteria and is in line with improved stewardship in healthcare.

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