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ABSTRACT: Background
Environmental pollutants, which coexist with allergens, have been associated with the exacerbation of asthma. However, the underlying molecular mechanisms remain elusive. We sought to determine whether benzo(a)pyrene (BaP) co-exposure with dermatophagoides group 1 allergen (Der f 1) can potentiate Der f 1-induced asthma and its underlying mechanisms.Methods
The effect of BaP was investigated in Der f 1-induced mouse model of asthma, including airway hyper-responsiveness, allergic inflammation, and epithelial-derived cytokines. The impact of BaP on Der f 1-induced airway epithelial cell oxidative stress (ROS) and cytokine release was further analyzed. The role of aryl hydrocarbon receptor (AhR) signaling in BaP-promoted Der f 1-induced ROS, cytokine production, and allergic inflammation was also investigated.Results
Compared with Der f 1, BaP co-exposure with Der f 1 led to airway hyper-responsiveness and increased lung inflammation in mouse model of asthma. Increased expression of TSLP, IL-33, and IL-25 was also found in the airways of these mice. Moreover, BaP co-exposure with Der f 1 activated AhR signaling with increased expression of AhR and CYP1A1 and promoted airway epithelial ROS generation and TSLP and IL-33, but not IL-25, expression. Interestingly, AhR antagonist CH223191 or cells with AhR knockdown abrogated the increased expression of ROS, TSLP, and IL-33. Furthermore, ROS inhibitor N-acetyl-L-cysteine (NAC) also suppressed BaP co-exposure-induced expression of epithelial TSLP, IL-33, and IL-25. Finally, AhR antagonist CH223191 and NAC inhibited BaP co-exposure with Der f 1-induced lung inflammation.Conclusions
Our findings suggest that BaP facilitates Der f 1-induced epithelial cytokine release through the AhR-ROS axis.
SUBMITTER: Wang E
PROVIDER: S-EPMC6790621 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Wang Eryi E Liu Xiaoyu X Tu Wei W Do Danh C DC Yu Haiqiong H Yang Liteng L Zhou Yufeng Y Xu Damo D Huang Shau-Ku SK Yang Pingchang P Ran Pixin P Gao Pei-Song PS Liu Zhigang Z
Allergy 20190619 9
<h4>Background</h4>Environmental pollutants, which coexist with allergens, have been associated with the exacerbation of asthma. However, the underlying molecular mechanisms remain elusive. We sought to determine whether benzo(a)pyrene (BaP) co-exposure with dermatophagoides group 1 allergen (Der f 1) can potentiate Der f 1-induced asthma and its underlying mechanisms.<h4>Methods</h4>The effect of BaP was investigated in Der f 1-induced mouse model of asthma, including airway hyper-responsivenes ...[more]