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Interleukin 33 Expression Induced by Aryl Hydrocarbon Receptor in Macrophages.
Toxicol Sci 2019; 170(2):404-414TS

Abstract

Polycyclic aromatic hydrocarbons (PAHs) contained in airborne particulate matter have been identified as a contributing factor for inflammation in the respiratory tract. Recently, interleukin-33 (IL-33) is strongly suggested to be associated with airway inflammation. Aryl hydrocarbon receptor (AhR) is a receptor for PAHs to regulate several metabolic enzymes, but the relationships between AhR and airway inflammation are still unclear. In this study, we examined the role of AhR in the expression of IL-33 in macrophages. THP-1 macrophages mainly expressed IL-33 variant 5, which in turn was strongly induced by the AhR agonists 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and kynurenine (KYN). AhR antagonist CH223191 suppressed the increase in IL-33 expression. Promoter analysis revealed that the IL-33 promoter has 2 dioxin response elements (DREs). AhR was recruited to both DREs after treatment with TCDD or KYN as assessed by gel shift and chromatin immunoprecipitation assays. A luciferase assay showed that one of the DREs was functional and involved in the expression of IL-33. Macrophages isolated from AhR-null mice expressed only low levels of IL-33 even in response to treatment with AhR ligands compared with wild-type cells. The treatment of THP-1 macrophages with diesel particulate matter and particle extracts increased the mRNA and protein expression of IL-33. Taken together, the results show that ligand-activated AhR mediates the induction of IL-33 in macrophages via a DRE located in the IL-33 promoter region. AhR-mediated IL-33 induction could be involved in the exacerbation and/or prolongation of airway inflammation elicited by toxic chemical substances.

Authors+Show Affiliations

Center for Health and the Environment, University of California, Davis 95616, California. Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Hiroshima 739-8521, Japan.Leibniz Research Institute for Environmental Medicine, Düsseldorf 40225, Germany.Center for Health and the Environment, University of California, Davis 95616, California. Department of Environmental Toxicology, University of California, Davis 95616, California. Air Resources Board, California Environmental Protection Agency, Sacramento 95812, California.Center for Health and the Environment, University of California, Davis 95616, California. Department of Environmental Toxicology, University of California, Davis 95616, California.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31093659

Citation

Ishihara, Yasuhiro, et al. "Interleukin 33 Expression Induced By Aryl Hydrocarbon Receptor in Macrophages." Toxicological Sciences : an Official Journal of the Society of Toxicology, vol. 170, no. 2, 2019, pp. 404-414.
Ishihara Y, Haarmann-Stemmann T, Kado NY, et al. Interleukin 33 Expression Induced by Aryl Hydrocarbon Receptor in Macrophages. Toxicol Sci. 2019;170(2):404-414.
Ishihara, Y., Haarmann-Stemmann, T., Kado, N. Y., & Vogel, C. F. A. (2019). Interleukin 33 Expression Induced by Aryl Hydrocarbon Receptor in Macrophages. Toxicological Sciences : an Official Journal of the Society of Toxicology, 170(2), pp. 404-414. doi:10.1093/toxsci/kfz114.
Ishihara Y, et al. Interleukin 33 Expression Induced By Aryl Hydrocarbon Receptor in Macrophages. Toxicol Sci. 2019 Aug 1;170(2):404-414. PubMed PMID: 31093659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin 33 Expression Induced by Aryl Hydrocarbon Receptor in Macrophages. AU - Ishihara,Yasuhiro, AU - Haarmann-Stemmann,Thomas, AU - Kado,Norman Y, AU - Vogel,Christoph F A, PY - 2019/5/17/pubmed PY - 2019/5/17/medline PY - 2019/5/17/entrez KW - AhR KW - IL-33 KW - diesel particulate matter KW - macrophages SP - 404 EP - 414 JF - Toxicological sciences : an official journal of the Society of Toxicology JO - Toxicol. Sci. VL - 170 IS - 2 N2 - Polycyclic aromatic hydrocarbons (PAHs) contained in airborne particulate matter have been identified as a contributing factor for inflammation in the respiratory tract. Recently, interleukin-33 (IL-33) is strongly suggested to be associated with airway inflammation. Aryl hydrocarbon receptor (AhR) is a receptor for PAHs to regulate several metabolic enzymes, but the relationships between AhR and airway inflammation are still unclear. In this study, we examined the role of AhR in the expression of IL-33 in macrophages. THP-1 macrophages mainly expressed IL-33 variant 5, which in turn was strongly induced by the AhR agonists 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) and kynurenine (KYN). AhR antagonist CH223191 suppressed the increase in IL-33 expression. Promoter analysis revealed that the IL-33 promoter has 2 dioxin response elements (DREs). AhR was recruited to both DREs after treatment with TCDD or KYN as assessed by gel shift and chromatin immunoprecipitation assays. A luciferase assay showed that one of the DREs was functional and involved in the expression of IL-33. Macrophages isolated from AhR-null mice expressed only low levels of IL-33 even in response to treatment with AhR ligands compared with wild-type cells. The treatment of THP-1 macrophages with diesel particulate matter and particle extracts increased the mRNA and protein expression of IL-33. Taken together, the results show that ligand-activated AhR mediates the induction of IL-33 in macrophages via a DRE located in the IL-33 promoter region. AhR-mediated IL-33 induction could be involved in the exacerbation and/or prolongation of airway inflammation elicited by toxic chemical substances. SN - 1096-0929 UR - https://www.unboundmedicine.com/medline/citation/31093659/Interleukin_33_expression_induced_by_aryl_hydrocarbon_receptor_in_macrophages L2 - https://academic.oup.com/toxsci/article-lookup/doi/10.1093/toxsci/kfz114 DB - PRIME DP - Unbound Medicine ER -