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

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.Peer reviewe

Ekonomisk åtstramning och kommunal förnyelse 1986-1987

This study forms part of a larger international project 'Fiscal Austerity and Urban Innovation' (FAUI). The purpose of the project is to study and analyse how and to what extent the tightening economic resources in society has resulted in changes and renewal within the scope of municipal operations. The questionnaire was directed to chief economic administrators and contained seven different parts: Budgeting and the budgeting process; Changes within the municipality; Planning and working routines; The municipality´s economic situation; Fiscal management strategies; Comparisons with other municipalities; and background information.I början av 1980-talet inleddes ett internationellt forskningssamarbete som kom att kallas 'Fiscal Austerity and Urban Innovation' (FAUI). Två sidor av den kommunala ekonomin bildade utgångspunkt för projektet, dels den kärvare ekonomin, dels de förändringar som uppkommit på lokal nivå, bland annat som ett resultat av de förändrade ekonomiska förutsättningarna. Projektet, som syftar till internationella jämförelser av hur kommunerna i olika länder agerat, bygger på enkätundersökningar av kommunala beslutsfattare. Totalt deltog forskare från ett femtiotal länder. Studien 'Ekonomisk åtstramning och kommunal förnyelse' utgör den svenska delen av projektet. Vid årsskiftet 1986/1987 skickades en enkät ut till ekonomicheferna i samtliga landets kommuner. Enkäten bestod av sju olika frågeområden: Budgetering och budgetarbete; Verksamhetsförändringar i kommunen; Planering och arbetssätt; Kommunens ekonomiska situation; Kommunalekonomiska åtgärder; Jämförelser med andra kommuner; samt bakgrundsuppgifter