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

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Iwona T. Myszor, Zahida Parveen, Håkan Ottosson, Peter Bergman, Birgitta Agerberth, Roger Strömberg, Gudmundur H. Gudmundsson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c34430d9332c4c8481c652a6656d4119
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c34430d9332c4c8481c652a6656d4119
record_format	dspace
spelling	oai:doaj.org-article:c34430d9332c4c8481c652a6656d41192021-12-02T16:08:42ZNovel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity10.1038/s41598-019-43350-z2045-2322https://doaj.org/article/c34430d9332c4c8481c652a6656d41192019-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-43350-zhttps://doaj.org/toc/2045-2322Abstract 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.Iwona T. MyszorZahida ParveenHåkan OttossonPeter BergmanBirgitta AgerberthRoger StrömbergGudmundur H. GudmundssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Iwona T. Myszor Zahida Parveen Håkan Ottosson Peter Bergman Birgitta Agerberth Roger Strömberg Gudmundur H. Gudmundsson Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
description	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.
format	article
author	Iwona T. Myszor Zahida Parveen Håkan Ottosson Peter Bergman Birgitta Agerberth Roger Strömberg Gudmundur H. Gudmundsson
author_facet	Iwona T. Myszor Zahida Parveen Håkan Ottosson Peter Bergman Birgitta Agerberth Roger Strömberg Gudmundur H. Gudmundsson
author_sort	Iwona T. Myszor
title	Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
title_short	Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
title_full	Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
title_fullStr	Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
title_full_unstemmed	Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
title_sort	novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/c34430d9332c4c8481c652a6656d4119
work_keys_str_mv	AT iwonatmyszor novelaroylatedphenylenediaminecompoundsenhanceantimicrobialdefenseandmaintainairwayepithelialbarrierintegrity AT zahidaparveen novelaroylatedphenylenediaminecompoundsenhanceantimicrobialdefenseandmaintainairwayepithelialbarrierintegrity AT hakanottosson novelaroylatedphenylenediaminecompoundsenhanceantimicrobialdefenseandmaintainairwayepithelialbarrierintegrity AT peterbergman novelaroylatedphenylenediaminecompoundsenhanceantimicrobialdefenseandmaintainairwayepithelialbarrierintegrity AT birgittaagerberth novelaroylatedphenylenediaminecompoundsenhanceantimicrobialdefenseandmaintainairwayepithelialbarrierintegrity AT rogerstromberg novelaroylatedphenylenediaminecompoundsenhanceantimicrobialdefenseandmaintainairwayepithelialbarrierintegrity AT gudmundurhgudmundsson novelaroylatedphenylenediaminecompoundsenhanceantimicrobialdefenseandmaintainairwayepithelialbarrierintegrity
_version_	1718384494079115264

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

Ejemplares similares