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Biochanin A enhances ROR gamma activity through STAT3-mediated recruitment of NCOA1
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| Title: | Biochanin A enhances ROR gamma activity through STAT3-mediated recruitment of NCOA1 |
| Authors: | Takahashi, Miki Browse this author | | Muromoto, Ryuta Browse this author →KAKEN DB | | Kojima, Hiroyuki Browse this author | | Takeuchi, Shinji Browse this author | | Kitai, Yuichi Browse this author →KAKEN DB | | Kashiwakura, Jun-ichi Browse this author | | Matsuda, Tadashi Browse this author →KAKEN DB |
| Keywords: | Isoflavones | | IL-17 | | STAT3 | | ROR gamma |
| Issue Date: | 5-Aug-2017 |
| Publisher: | Elsevier |
| Journal Title: | Biochemical and biophysical research communications |
| Volume: | 489 |
| Issue: | 4 |
| Start Page: | 503 |
| End Page: | 508 |
| Publisher DOI: | 10.1016/j.bbrc.2017.05.181 |
| PMID: | 28579428 |
| Abstract: | Interleukin (IL)-17-producing T cells play important roles in autoimmunity, chronic inflammation and host protection against extracellular bacteria and fungi. The retinoic acid receptor-related orphan receptors (ROR) alpha and beta are key regulators of the IL-17-producing phenotype. We previously showed that the isoflavone biochanin A enhanced ROR-mediated transcriptional activity. Here, we investigated the possible mechanisms underlying this ROR activation. Biochanin A-treated murine thymoma EL4 and primary splenocytes demonstrated enhanced induction of IL-17. Biochanin A also induced tyrosine-phosphorylation of signal transducer and activator of transcription 3 (STAT3) in these cells. Stable knockdown of either ROR gamma or STAT3 in EL4 cells canceled biochanin A-induced upregulation of IL-17 expression. Importantly, biochanin A enhanced complex formation between ROR gamma and STAT3 or nuclear-receptor coactivator 1 (NCOA1). Furthermore, the biochanin A-induced ROR gamma-NCOA1 complex was disrupted by a dominant negative mutant of STAT3 or by the STAT3 specific inhibitor Stattic. These results suggest that biochanin A activates ROR gamma-dependent IL-17 transcription through the enhancement of STAT3 phosphorylation and STAT3-mediated recruitment of NCOA1 to ROR gamma. (C) 2017 Elsevier Inc. All rights reserved. |
| Rights: | ©2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/71218 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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