Aryl hydrocarbon receptor activation by diesel exhaust particles mediates epithelium-derived cytokines expression in severe allergic asthma

C. M. Weng, C. H. Wang, M. J. Lee, J. R. He, H. Y. Huang, M. W. Chao, K. F. Chung, Han-Pin Kuo

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2192-2204
Number of pages13
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume73
Issue number11
DOIs
Publication statusPublished - Nov 1 2018

Keywords

  • aryl hydrocarbon receptor
  • diesel exhaust particles
  • epithelium-derived cytokines
  • severe asthma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Aryl hydrocarbon receptor activation by diesel exhaust particles mediates epithelium-derived cytokines expression in severe allergic asthma'. Together they form a unique fingerprint.

Cite this