A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor

Abstract Chronic exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is associated with asthma, but its regulatory mechanisms remain incompletely defined. We report herein that elevated levels of urinary 1-hydroxypyrene, a biomarker of PAH exposure, were found in asthmatic subjects (n = 39)...

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Autores principales:	Tzu-Hsuan Wong, Chon-Lin Lee, Hsiang-Han Su, Chin-Lai Lee, Chao-Chien Wu, Chin-Chou Wang, Chau-Chyun Sheu, Ruay-Sheng Lai, Sum-Yee Leung, Chi-Cheng Lin, Yu-Feng Wei, Chien-Jen Wang, Yu-Chun Lin, Hua-Ling Chen, Ming-Shyan Huang, Jeng-Hsien Yen, Shau-Ku Huang, Jau-Ling Suen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a0379ce7611248c0a83dc40bde2a7d25
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spelling	oai:doaj.org-article:a0379ce7611248c0a83dc40bde2a7d252021-12-02T15:08:23ZA prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor10.1038/s41598-018-23542-92045-2322https://doaj.org/article/a0379ce7611248c0a83dc40bde2a7d252018-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23542-9https://doaj.org/toc/2045-2322Abstract Chronic exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is associated with asthma, but its regulatory mechanisms remain incompletely defined. We report herein that elevated levels of urinary 1-hydroxypyrene, a biomarker of PAH exposure, were found in asthmatic subjects (n = 39) as compared to those in healthy subjects (n = 43) living in an industrial city of Taiwan, where indeno[1,2,3-cd]pyrene (IP) was found to be a prominent PAH associated with ambient PM2.5. In a mouse model, intranasal exposure of mice with varying doses of IP significantly enhanced antigen-induced allergic inflammation, including increased airway eosinophilia, Th2 cytokines, including IL-4 and IL-5, as well as antigen-specific IgE level, which was absent in dendritic cell (DC)-specific aryl hydrocarbon receptor (AhR)-null mice. Mechanistically, IP treatment significantly altered DC’s function, including increased level of pro-inflammatory IL-6 and decreased generation of anti-inflammatory IL-10. The IP’s effect was lost in DCs from mice carrying an AhR-mutant allele. Taken together, these results suggest that chronic exposure to environmental PAHs may pose a significant risk for asthma, in which IP, a prominent ambient PAH in Taiwan, was shown to enhance the severity of allergic lung inflammation in mice through, at least in part, its ability in modulating DC’s function in an AhR-dependent manner.Tzu-Hsuan WongChon-Lin LeeHsiang-Han SuChin-Lai LeeChao-Chien WuChin-Chou WangChau-Chyun SheuRuay-Sheng LaiSum-Yee LeungChi-Cheng LinYu-Feng WeiChien-Jen WangYu-Chun LinHua-Ling ChenMing-Shyan HuangJeng-Hsien YenShau-Ku HuangJau-Ling SuenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tzu-Hsuan Wong Chon-Lin Lee Hsiang-Han Su Chin-Lai Lee Chao-Chien Wu Chin-Chou Wang Chau-Chyun Sheu Ruay-Sheng Lai Sum-Yee Leung Chi-Cheng Lin Yu-Feng Wei Chien-Jen Wang Yu-Chun Lin Hua-Ling Chen Ming-Shyan Huang Jeng-Hsien Yen Shau-Ku Huang Jau-Ling Suen A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
description	Abstract Chronic exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is associated with asthma, but its regulatory mechanisms remain incompletely defined. We report herein that elevated levels of urinary 1-hydroxypyrene, a biomarker of PAH exposure, were found in asthmatic subjects (n = 39) as compared to those in healthy subjects (n = 43) living in an industrial city of Taiwan, where indeno[1,2,3-cd]pyrene (IP) was found to be a prominent PAH associated with ambient PM2.5. In a mouse model, intranasal exposure of mice with varying doses of IP significantly enhanced antigen-induced allergic inflammation, including increased airway eosinophilia, Th2 cytokines, including IL-4 and IL-5, as well as antigen-specific IgE level, which was absent in dendritic cell (DC)-specific aryl hydrocarbon receptor (AhR)-null mice. Mechanistically, IP treatment significantly altered DC’s function, including increased level of pro-inflammatory IL-6 and decreased generation of anti-inflammatory IL-10. The IP’s effect was lost in DCs from mice carrying an AhR-mutant allele. Taken together, these results suggest that chronic exposure to environmental PAHs may pose a significant risk for asthma, in which IP, a prominent ambient PAH in Taiwan, was shown to enhance the severity of allergic lung inflammation in mice through, at least in part, its ability in modulating DC’s function in an AhR-dependent manner.
format	article
author	Tzu-Hsuan Wong Chon-Lin Lee Hsiang-Han Su Chin-Lai Lee Chao-Chien Wu Chin-Chou Wang Chau-Chyun Sheu Ruay-Sheng Lai Sum-Yee Leung Chi-Cheng Lin Yu-Feng Wei Chien-Jen Wang Yu-Chun Lin Hua-Ling Chen Ming-Shyan Huang Jeng-Hsien Yen Shau-Ku Huang Jau-Ling Suen
author_facet	Tzu-Hsuan Wong Chon-Lin Lee Hsiang-Han Su Chin-Lai Lee Chao-Chien Wu Chin-Chou Wang Chau-Chyun Sheu Ruay-Sheng Lai Sum-Yee Leung Chi-Cheng Lin Yu-Feng Wei Chien-Jen Wang Yu-Chun Lin Hua-Ling Chen Ming-Shyan Huang Jeng-Hsien Yen Shau-Ku Huang Jau-Ling Suen
author_sort	Tzu-Hsuan Wong
title	A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
title_short	A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
title_full	A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
title_fullStr	A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
title_full_unstemmed	A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
title_sort	prominent air pollutant, indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a0379ce7611248c0a83dc40bde2a7d25
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A prominent air pollutant, Indeno[1,2,3-cd]pyrene, enhances allergic lung inflammation via aryl hydrocarbon receptor

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