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 4weeks
after treatment. Thus, our data suggests that IL-24 is a pulmonary exposure target
cytokine of environmental AhR agonists.