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Cited by 50Asthma and respiratory diseasesToxic Organic Pollutants ImpactAir Quality and Health Impacts

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

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Wong, Tzu-Hsuan, Lee, Chon-Lin, Su, Hsiang-Han, Lee, Chin-Lai, Wu, Chao-Chien, Wang, Chin-Chou, Sheu, Chau-Chyun, Lai, Ruay-Sheng +10 more·2018·Scientific Reports
DOI 10.1038/s41598-018-23542-9PMC PMC5979946
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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 PM 2.5. 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.

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  • This mouse continues to be widely used as a nonresponsive control for studies examining the AHR-mediated effects of ligands like TCDD and BaP on common end points such as carcinogenesis and inflammation.

    “This mouse continues to be widely used as a nonresponsive control for studies examining the AHR-mediated effects of ligands like TCDD and BaP on common end points such as carcinogenesis and inflammation (Kennedy et al., 2014; Wong et al., 2018).”

    From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Wong et al., 2018

    The Methods (Mice; page not provided) and Results (IP exposure modulated DC’s function in an AhR-dependent manner; page not provided) show that the paper used AhRd mice as low-responder comparators in experiments on IP and allergic inflammation. It does not establish that these mice are widely used as nonresponsive controls, or that they were used to study TCDD, BaP, or carcinogenesis. (LLM, conf=0.86)

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Cited by

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Authors
Wong, T.-H., Lee, C.-L., Su, H.-H., Lee, C.-L., Wu, C.-C., Wang, C.-C., Sheu, C.-C., Lai, R.-S., Leung, S.-Y., Lin, C.-C., Wei, Y.-F., Wang, C.-J., Lin, Y.-C., Chen, H.-L., Huang, M.-S., Yen, J.-H., Huang, S.-K., & Suen, J.-L.
Affiliations
  • Kaohsiung Medical University (TW)
  • National Sun Yat-sen University (TW)
  • Chang Gung University (TW)
  • Kaohsiung Veterans General Hospital (TW)
  • E-Da Hospital (TW)
  • National Health Research Institutes (TW)
  • Johns Hopkins University (US)
Corresponding author
Suen, Jau-Ling
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-03-26
Volume
8
Issue
1
Pages
5198-5198
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-23542-9
PMC
PMC5979946
OpenAlex
W2794464191
Cited by
50
References
1
Citations by year
2026: 5 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 3 · 2019: 4 · 2018: 2
FWCI
2.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Veterans Affairs (CDA 10-014)
  • National Science Council (MOST 105)
  • Ministry of Science and Technology, Taiwan (MOST106-2314-B037-072, MOST105-2320-B037-015, MOST106-2320-B037-018)
  • Kaohsiung Medical University (KMU-SH000184, KMU-TP104A05)
  • National Health Research Institutes (EOPP10-014, EOSP07-014)
Topics
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
Keywords
indeno[1,2,3-cd]pyrene, polycyclic aromatic hydrocarbons, aryl hydrocarbon receptor, asthma, allergic airway inflammation, dendritic cells, 1-hydroxypyrene, PM2.5, Th2 cytokines, IL-4, IL-5, interleukin-6, IL-10, IgE, airway eosinophilia, air pollution
MeSH terms
Adolescent, Adult, Air Pollutants, Animals, Asthma, Dendritic Cells, Female, Humans, Hypersensitivity, Lung, Male, Middle Aged, Pneumonia, Pyrenes, Taiwan, Receptors, Aryl Hydrocarbon, Mice, Particulate Matter, Young Adult

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