title: Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung.
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 4weeks after treatment. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonists.
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yueh-Hsia
authors.initials: YH
authors.lastname: Luo
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Ho
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Hui-Ti
authors.initials: HT
authors.lastname: Tsai
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Taiwan. Electronic address: pplin@nhri.org.tw.
authors.forename: Pinpin
authors.initials: P
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists*; D000099180:Interleukin-24
chemical_list: D016207:Cytokines; D006846:Hydrocarbons, Halogenated; D018336:Receptors, Aryl Hydrocarbon; C431904:Il24 protein, mouse; D000099180:Interleukin-24
keywords: Aryl hydrocarbon receptor; Cytokines; Environmental aryl hydrocarbon receptor agonists; Interleukin (IL)-24; Particulate matter; Polycyclic aromatic hydrocarbons