@article{b198a6e1c0764fe3a4b30a0c24554262,
title = "Aryl hydrocarbon receptor activation by diesel exhaust particles mediates epithelium-derived cytokines expression in severe allergic asthma",
abstract = "BACKGROUND Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium-derived thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma. METHODS Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles (DEP) to determine AhR-mediated IL-33, Il-25 and TSLP synthesis and release. RESULTS Primary bronchial epithelial cells exposed to DEP showed up-regulation of IL-33, IL-25 and TSLP. These effects were abolished by knock-down of AhR by siRNA. Increased AhR/ARNT binding to promoters of IL-33, IL-25, and TSLP was found using chromatin immunoprecipitation (ChIP) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL-33, IL-25 and TSLP. These patients derived clinical benefit from anti-IgE treatment. CONCLUSION AhR activation by DEP mediates up-regulation of IL-33, IL-25 and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma. This article is protected by copyright. All rights reserved.",
keywords = "aryl hydrocarbon receptor, diesel exhaust particles, epithelium-derived cytokines, severe asthma",
author = "Weng, {C. M.} and Wang, {C. H.} and Lee, {M. J.} and He, {J. R.} and Huang, {H. Y.} and Chao, {M. W.} and Chung, {K. F.} and Han-Pin Kuo",
note = "Funding Information: H-P Kuo is a consultant for Norvatis, Taiwan, a speaker for GSK, Norvatis, Elli Lily, Pfizer, Roche, Boehringer Ingelheim, Astra-Zeneca, Sanofi-Aventis, and MSD, and has received research grants from Elli Lily, Sanofi-Aventis, Roche, Astra-Zeneca, and GSK. K F Chung has consulted for Gilead, has been on Advisory Boards of Merck and GSK, and has received grants from UK Medical Research Council, Asthma UK, and the Wellcome Trust. The other authors have no financial disclosures. Funding Information: Funding information This study was supported by Taiwan Ministry of Science and Technology grant, 103-2314-B-182A-091-MY3 and Chang Gung Medical Foundation OMRP. We also thank the Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, for their technical assistance. Funding Information: This study was supported by Taiwan Ministry of Science and Technology grant, 103-2314-B-182A-091-MY3 and Chang Gung Medical Foundation OMRP. Publisher Copyright: {\textcopyright} 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.",
year = "2018",
month = nov,
day = "1",
doi = "10.1111/all.13462",
language = "English",
volume = "73",
pages = "2192--2204",
journal = "Allergy: European Journal of Allergy and Clinical Immunology",
issn = "0105-4538",
publisher = "Wiley-Blackwell",
number = "11",
}