Evidence map›Paper›PMID 25583575›Full record

ArticleToxicology2015

Isoflavones enhance interleukin-17 gene expression via retinoic acid receptor-related orphan receptors α and γ.

Hiroyuki Kojima, Yukimasa Takeda, Ryuta Muromoto, Miki Takahashi, Toru Hirao, Shinji Takeuchi, Anton M Jetten, Tadashi Matsuda

Open access · greenAbstract read
In one paragraph

Article in Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Isoflavones and inflammatory bowel disease.World journal of clinical cases · 2020
    Review
  8. Review
  9. Article
  10. Digoxin, an Overlooked Agonist of RORγ/RORγT.Frontiers in pharmacology · 2018
    Article
  11. Review
  12. Article
  13. Article
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Hiroyuki KojimaHokkaido Institute of Public Health, Kita-19, Nishi-12, Kita-ku, Sapporo 060-0819, Japan. Electronic address: kojima@iph.pref.hokkaido.jp.
Yukimasa TakedaNational Institute of Environmental Health Sciences, National Institutes of Health, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Ryuta MuromotoGraduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Miki TakahashiGraduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Toru HiraoGraduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Shinji TakeuchiHokkaido Institute of Public Health, Kita-19, Nishi-12, Kita-ku, Sapporo 060-0819, Japan.
Anton M JettenNational Institute of Environmental Health Sciences, National Institutes of Health, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA.
Tadashi MatsudaGraduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Hokkaido University · JPHokkaido Institute of Public Health · JPNational Institutes of Health · US

Funding

Nuclear receptors: action, functions, and roles in diseaseZIAES101586 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JETTEN, ANTON M · 2009 to 2025
$13.5M
Nuclear receptors--Action, functions, &roles in diseaseZ01ES101586 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JETTEN, ANTON M · 2003 to 2008
$3.2M
Mechanism Of Action And Functions Of The Gli-related Proteins Glis 1-3Z01ES100485 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI JETTEN, ANTON M · 2002 to 2008
$2.3M
Intramural NIH HHS Z01 ES100485Intramural NIH HHS Z01 ES101586
6 · The paper itself

Abstract

The retinoic acid receptor-related orphan receptors α and γ (RORα and RORγ), are key regulators of helper T (Th)17 cell differentiation, which is involved in the innate immune system and autoimmune disorders. In this study, we investigated the effects of isoflavones on RORα/γ activity and the gene expression of interleukin (IL)-17, which mediates the function of Th17 cells. In doxycycline-inducible CHO stable cell lines, we found that four isoflavones, biochanin A (BA), genistein, formononetin, and daidzein, enhanced RORα- or RORγ-mediated transcriptional activity in a dose-dependent manner. In an activation assay of the Il17a promoter using Jurkat cells, these compounds enhanced the RORα- or RORγ-mediated activation of the Il17a promoter at concentrations of 1 × 10(-6)M to 1 × 10(-5)M. In mammalian two-hybrid assays, the four isoflavones enhanced the interaction between the RORα- or RORγ-ligand binding domain and the co-activator LXXLL peptide in a dose-dependent manner. In addition, these isoflavones potently enhanced Il17a mRNA expression in mouse T lymphoma EL4 cells treated with phorbol myristate acetate and ionomycin, but showed slight enhancement of Il17a gene expression in RORα/γ-knockdown EL4 cells. Immunoprecipitation and immunoblotting assays also revealed that BA enhanced the interaction between RORγt and SRC-1, which is a co-activator for nuclear receptors. Taken together, these results suggest that the isoflavones have the ability to enhance IL-17 gene expression by stabilizing the interactions between RORα/γ and co-activators. This also provides the first evidence that dietary chemicals can enhance IL-17 gene expression in immune cells.

Indexed as

AnimalsCell DifferentiationCell Line, TumorCHO CellsCricetinaeCricetulusGene Expression RegulationGenisteinHeLa CellsHumansInterleukin-17IsoflavonesJurkat CellsMiceNuclear Receptor Subfamily 1, Group F, Member 1Nuclear Receptor Subfamily 1, Group F, Member 3biochanin AdaidzeinformononetinGenisteinInterleukin-17IsoflavonesNuclear Receptor Subfamily 1, Group F, Member 1Nuclear Receptor Subfamily 1, Group F, Member 3Receptors, Cytoplasmic and NuclearRNA, MessengerInterleukin 17IsoflavoneLuciferase assayRetinoic acid receptor-related orphan receptorTh17

Identifiers

PMID25583575
PMCPMC5877804
OpenAlexW2088528767

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.