Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung
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. - Graphical abstract: (A) Cytokine and chemokine gene expressions were examined in CL5 cells treated with AhR and non-AhR agonists. Thirteen cytokines and chemokines genes were altered in the AhR agonist-treated cells, but not in the non-AhR agonist-treated cells. IL-24 was the most highly induced gene among the AhR-modulated cytokines. (B) Both AhR agonists and PM{sub 2.5} induced IL-24 production in the CL5 cells and macrophages. Cotreatment with an AhR antagonist (DMF) or transfections with shRNA for AhR abolished IL-24 induction by BaP in CL5 cells. Intratracheal instillation of PM activated AhR-mediated inflammatory responses and IL-24 expression in mouse lungs. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonist. - Highlights: • IL-24 is identified as a target cytokine of environmental AhR agonist exposure. • AhR agonists increased IL-24 expression in an AhR-dependent manner in lung cells. • Ambient particulate matter induces IL-24 secretion in BALF in mice. • IL-24 can be used to evaluate environmental lung diseases.
- OSTI ID:
- 22690980
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 324; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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