Benzo(a)pyrene facilitates dermatophagoides group 1 (Der f 1)-induced epithelial cytokine release through aryl hydrocarbon receptor in asthma

Eryi Wang, Xiaoyu Liu, Wei Tu, Danh C. Do, Haiqiong Yu, Liteng Yang, Yufeng Zhou, Damo Xu, Shau Ku Huang, Pingchang Yang, Pixin Ran, Pei Song Gao, Zhigang Liu

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1675-1690
Number of pages16
JournalAllergy
Volume74
Issue number9
DOIs
Publication statusPublished - Sep 1 2019
Externally publishedYes

Keywords

  • Aryl hydrocarbon receptor
  • benzo(a)pyrene (BaP)
  • dermatophagoides group 1 allergen (Der f 1)
  • IL-25
  • IL-33
  • reactive oxygen species
  • TSLP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, E., Liu, X., Tu, W., Do, D. C., Yu, H., Yang, L., Zhou, Y., Xu, D., Huang, S. K., Yang, P., Ran, P., Gao, P. S., & Liu, Z. (2019). Benzo(a)pyrene facilitates dermatophagoides group 1 (Der f 1)-induced epithelial cytokine release through aryl hydrocarbon receptor in asthma. Allergy, 74(9), 1675-1690. https://doi.org/10.1111/all.13784