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

Chin-Lai Lee,Jau-Ling Suen,Ruay-Sheng Lai,Tzu-Hsuan Wong,Hua-Ling Chen,Chi-Cheng Lin,Chien-Jen Wang,Yu-Feng Wei,Jeng-Hsien Yen,Shau-Ku Huang,Chon-Lin Lee,Ming-Shyan Huang,Hsiang-Han Su,Yu-Chun Lin,Chin-Chou Wang,Chau-Chyun Sheu,Sum-Yee Leung,Chao-Chien Wu

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.

Highlights

Asthma is a common chronic airway inflammatory disease characterized by airway obstruction, bronchial hyper-responsiveness and airway inflammation[1]
We demonstrated that indeno[1,2,3-cd]pyrene (IP) was the major component of ambient Polycyclic aromatic hydrocarbons (PAHs) in Kaohsiung City in Taiwan, and that IP exposure exacerbated antigen-induced pulmonary inflammation in a mouse model of asthma and the IP’s effect was, at least in part, mediated by its impact on dendritic cell (DC)’s function in an Aryl hydrocarbon receptor (AhR)-dependent manner
Results showed that among the 16 PAHs analyzed, IP was a prominent PAH associated with ambient PM2.5 in all sites (Fig. 1A) and all seasons

Summary

Introduction

Asthma is a common chronic airway inflammatory disease characterized by airway obstruction, bronchial hyper-responsiveness and airway inflammation[1]. AhR is originally discovered as a high affinity receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); it has been recognized as a receptor for many environmental pollutants, including benzo[a]pyrene (BaP). They can directly bind to AhR and trigger its translocation into nucleus to mediate the downstream effects, including detoxification and other cellular responses[12]. The ligand-AhR axis is shown to be critical in controlling the growth and function of mast cells in a calcium (Ca2+)- and reactive oxygen species (ROS)-dependent fashion[15,16]

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