Biochanin A enhances ROR gamma activity through STAT3-mediated recruitment of NCOA1

Takahashi, Miki; Muromoto, Ryuta; Kojima, Hiroyuki; Takeuchi, Shinji; Kitai, Yuichi; Kashiwakura, Jun-ichi; Matsuda, Tadashi

Biochanin A enhances ROR gamma activity through STAT3-mediated recruitment of NCOA1

Takahashi, Miki; Muromoto, Ryuta; Kojima, Hiroyuki et al.

Biochemical and biophysical research communications, 2017, 489(4), 503-508

Permalink : https://hdl.handle.net/2115/71218

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アクセス権	open access
URI	https://hdl.handle.net/2115/71218
タイトル	Biochanin A enhances ROR gamma activity through STAT3-mediated recruitment of NCOA1
著者	Takahashi, Miki ; Muromoto, Ryuta ; Kojima, Hiroyuki ; Takeuchi, Shinji ; Kitai, Yuichi ; Kashiwakura, Jun-ichi ; Matsuda, Tadashi
著者名 Takahashi, Miki
e-Rad_Researcher 30455597 著者名 Muromoto, Ryuta
著者名 Kojima, Hiroyuki
著者名 Takeuchi, Shinji
e-Rad_Researcher 90756165 著者名 Kitai, Yuichi
著者名 Kashiwakura, Jun-ichi
e-Rad_Researcher 20212219 著者名 Matsuda, Tadashi
言語	英語
キーワード	Isoflavones
	IL-17
	STAT3
	ROR gamma
発行日	2017-08-05
出版者	Elsevier
収録物名	Biochemical and biophysical research communications
巻(号)	489(4)
ページ	503-508
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©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/
PISSN	0006-291X
関連情報	PMID 28579428
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.bbrc.2017.05.181