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Aryl hydrocarbon receptor activation by diesel exhaust particles mediates epithelium‐derived cytokines expression in severe allergic asthma
Author(s) -
Weng C.M.,
Wang C.H.,
Lee M.J.,
He J.R.,
Huang H.Y.,
Chao M.W.,
Chung K. F.,
Kuo H.P.
Publication year - 2018
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13462
Subject(s) - thymic stromal lymphopoietin , aryl hydrocarbon receptor , immunology , downregulation and upregulation , cytokine , interleukin 22 , chromatin immunoprecipitation , gene knockdown , interleukin 13 , interleukin , medicine , chemistry , gene expression , promoter , transcription factor , apoptosis , gene , biochemistry
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 upregulation of IL ‐33, IL ‐25, and TSLP . These effects were abolished by knockdown of AhR by si RNA . Increased AhR/ ARNT binding to promoters of IL ‐33, IL ‐25, and TSLP was found using chromatin immunoprecipitation (Ch IP ) 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 Aryl hydrocarbon receptor activation by DEP mediates upregulation of IL ‐33, IL ‐25, and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma.

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