Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung

Yueh Hsia Luo, Yu Chun Kuo, Ming Hsien Tsai, Chia Chi Ho, Hui Ti Tsai, Chin Yu Hsu, Yu Cheng Chen, Pinpin Lin

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Exposure to environmental aryl hydrocarbon receptor (AhR) agonists, such as halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs), has great impacts on the development of various lung diseases. As emerging molecular targets for AhR agonists, cytokines may contribute to the inflammatory or immunotoxic effects of environmental AhR agonists. However, general cytokine expression may not specifically indicate environmental AhR agonist exposure. By comparing cytokine and chemokine expression profiles in human lung adenocarcinoma cell line CL5 treated with AhR agonists and the non-AhR agonist polychlorinated biphenyl (PCB) 39, we identified a target cytokine of environmental AhR agonist exposure of in the lungs. Thirteen cytokine and chemokine genes were altered in the AhR agonists-treated cells, but none were altered in the PCB39-treated cells. Interleukin (IL)-24 was the most highly induced gene among AhR-modulated cytokines. Cotreatment with AhR antagonist completely prevented IL-24 induction by AhR agonists in the CL5 cells. Knockdown AhR expression with short-hairpin RNA (shRNA) significantly reduced benzo[a]pyrene (BaP)-induced IL-24 mRNA levels. We further confirmed that gene transcription, but not mRNA stability, was involved in IL-24 upregulation by BaP. Particulate matter (PM) in the ambient air contains some PAHs and is reported to activate AhR. Oropharyngeal aspiration of PM significantly increased IL-24 levels in lung epithelia and in bronchoalveolar lavage fluid of mice 4 weeks after treatment. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonists.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalToxicology and Applied Pharmacology
Volume324
DOIs
StatePublished - 1 Jun 2017

Keywords

  • Aryl hydrocarbon receptor
  • Cytokines
  • Environmental aryl hydrocarbon receptor agonists
  • Interleukin (IL)-24
  • Particulate matter
  • Polycyclic aromatic hydrocarbons

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