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http://ir.nhri.org.tw/handle/3990099045/10102
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| Title: | Epigenetic synergism between interleukin-4 and aryl-hydrocarbon receptor in human macrophages |
| Authors: | Liao, WT;Lu, JH;Wang, WT;Hung, CH;Sheu, CC;Huang, SK |
| Contributors: | National Institute of Environmental Health Sciences |
| Abstract: | 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-gamma/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-gamma/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-gamma/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. KEY MESSAGE: Human CCL1 gene is selectively targeted by AhR in M(IL-4) macrophage. IL-4-induced epigenetic modification potentiates AhR-mediated CCL1 expression. This epigenetic control of CCL1 expression is not operative in murine macrophages. |
| Date: | 2017-04 |
| Relation: | Journal of Molecular Medicine. 2017 Apr;95(4):395-404. |
| Link to: | http://dx.doi.org/10.1007/s00109-016-1493-1 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0946-2716&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000398516800006 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84997077999 |
| Appears in Collections: | [黃嘯谷] 期刊論文
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| PUB27888289.pdf | | 1027Kb | Adobe PDF | 389 | View/Open |
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