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Epigenetic synergism between interleukin-4 and aryl-hydrocarbon receptor in human macrophages
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نویسنده
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Liao Wei-Ting ,Lu Jian-He ,Wang Wei-Ting ,Hung Chih-Hsing ,Sheu Chau-Chyun ,Huang Shau-Ku
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منبع
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journal of molecular medicine - 2017 - دوره : 95 - شماره : 4 - صفحه:395 -404
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چکیده
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The aryl hydrocarbon receptor (ahr)-ligand axis is involved in immune regulation, but its molecular basis remains to be fully elucidated. chemokine (c-c motif) ligand 1 (ccl1) is an important chemoattractant, but how ccl1 is regulated remains to be defined. the role of ahr in regulating ccl1 expression in two major subsets of macrophage was investigated. we used a human thp-1 cell line, monocytes, and mouse peritoneal macrophages to generate m(ifn-γ/lps) and m(il-4) subsets, and the ahr’s ligand effect was determined by the use of a combination of chromatin immunoprecipitation, pcr, and elisa. upon exposure to a classical ahr ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd), selective induction of ccl1 was noted only in m(il-4), not m(ifn-γ/lps) cells in human but not murine macrophages. this selectivity was mediated by ahr’s binding to the distal dioxin-responsive element (dre) in the ccl1 promoter of the m(il-4) subset, and a deletion mutant lacking the distal dre sequence lost its activity. in contrast to the m(ifn-γ/lps) cells, the distal dre was devoid of tri-methylated histone 3 lysine 27 (h3k27) in m(il-4) cells, and the addition of a h3k27 demethylase inhibitor blocked ahr-mediated ccl1 expression. similar selectivity of ccl1 expression was also noted in monocyte-derived m(il-4) subsets, and the level of ahr binding to distal dre in monocytes was correlated with the levels of plasma interleukin-4 (il-4) in 23 human subjects. these findings suggested the existence of a new regulatory epigenetic-based mechanism, wherein ahr in concert with il-4 differentially regulated human, not murine, macrophage ccl1 response.
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کلیدواژه
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Aryl hydrocarbon receptor ,Dioxin ,Macrophage polarization ,Chemokine C-C motif ligand 1
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آدرس
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Kaohsiung Medical University, Department of Biotechnology, Taiwan. National Sun Yat-Sen University, Department of Biological Sciences, Taiwan, Kaohsiung Medical University, Taiwan, Kaohsiung Medical University, Department of Biotechnology, Taiwan, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Department of Pediatrics, Taiwan. Kaohsiung Medical University, Department of Pediatrics, Taiwan, Kaohsiung Medical University Hospital, Department of Internal Medicine, Taiwan. Kaohsiung Medical University, Department of Internal Medicine, Taiwan, National Health Research Institutes, Taiwan. Johns Hopkins University, USA. Kaohsiung Medical University, Taiwan
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Authors
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