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Biochanin A enhances ROR gamma activity through STAT3-mediated recruitment of NCOA1
- Source :
- Biochemical and biophysical research communications. 489(4):503-508
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
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.
- Subjects :
- STAT3
IL-17
ROR gamma
Isoflavones
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 489
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.jairo.........b447ea345726481962321e60ddc5504b