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

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

  • Sci Rep. 2018 Mar 26;8(1):5198. doi: 10.1038/s41598-018-23542-9.
Tzu-Hsuan Wong 1,  Chon-Lin Lee 2 3,  Hsiang-Han Su 1,  Chin-Lai Lee 1,  Chao-Chien Wu 4,  Chin-Chou Wang 4 5,  Chau-Chyun Sheu 3 6 7,  Ruay-Sheng Lai 8,  Sum-Yee Leung 4,  Chi-Cheng Lin 9,  Yu-Feng Wei 10,  Chien-Jen Wang 11,  Yu-Chun Lin 11,  Hua-Ling Chen 11,  Ming-Shyan Huang 6 7,  Jeng-Hsien Yen 1 12,  Shau-Ku Huang 1 3 11 13 14,  Jau-Ling Suen 15 16 17
Affiliations

Affiliations

  • 1 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 2 Department of Marine Environment and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan.
  • 3 Research Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 4 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan.
  • 5 Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 6 Divison of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 7 College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 8 Division of Chest Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
  • 9 Chest Division, Department of Internal Medicine, Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Ping-Tung, Taiwan.
  • 10 Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
  • 11 National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
  • 12 Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 13 Lou-Hu Hospital, Shen-Zhen University, Shen-Zhen, China.
  • 14 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 15 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. jlsuen@kmu.edu.tw.
  • 16 Research Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. jlsuen@kmu.edu.tw.
  • 17 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. jlsuen@kmu.edu.tw.
PMID: 29581487 DOI: 10.1038/s41598-018-23542-9
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.

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