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

Autor: Birgitta Agerberth, Peter Bergman, Roger Strömberg, Iwona T Myszor, Zahida Parveen, Gudmundur H. Gudmundsson, Håkan Ottosson
Přispěvatelé: Lífvísindasetur (HÍ), Biomedical Center (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Háskóli Íslands, University of Iceland, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI)
Rok vydání: 2019
Předmět:
0301 basic medicine
Pyridines
medicine.medical_treatment
Gene Expression
Phenylenediamines
Cathelicidin
chemistry.chemical_compound
0302 clinical medicine
Ónæmisfræði
Innate immunity
Multidisciplinary
Entinostat
Effector
musculoskeletal
neural
and ocular physiology
Antimicrobial Peptide LL 37
Cell biology
Anti-Bacterial Agents
Frumulíffræði
Benzamides
Pseudomonas aeruginosa
cardiovascular system
Medicine
Signal transduction
Cell signalling
STAT3 Transcription Factor
Cell signaling
Cell Survival
Science
Bronchi
Article
Cell Line
03 medical and health sciences
Immunity
Cathelicidins
medicine
Humans
Pseudomonas Infections
Innate immune system
Ónæmiserfðafræði
Tumor Necrosis Factor-alpha
Interleukin-8
Epithelial Cells
Immunity
Innate
030104 developmental biology
chemistry
STAT protein
030217 neurology & neurosurgery
Antimicrobial Cationic Peptides
Zdroj: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
ISSN: 2045-2322
Popis: Publisher's version (útgefin grein)
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.
Icelandic Center for Research (RANNÍS 173931) and University of Iceland research fund are acknowledged for support. Bryndís Valdimarsdóttir for advises on preparation of conditioned media and cell culture. Kristín Elísabet Alansdóttir for help with confocal microscopy and ImageJ analyses. Thanks to Náttúruverndarsjóður Pálma Jónssonar for early support of this project. We acknowledge Prof. Ronald G. Crystal and collaborators for generously providing us with the BCi-NS1.1 cell line. We thank Snæbjörn Pálsson for advices on statistical analysis.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje