Objectives: The purpose of this study was to explore the potential of the bromodomain and extra-terminal domain (BET) bromodomain to regulate IL-17 expression in peripheral blood from patients with rheumatoid arthritis (RA) and its underlying mechanisms. Methods: The level of IL-17A, TNFα and IFNγ in PBMCs from patients with RA was evaluated by a cytometric bead array. The IL-17A and IFNγ production in the supernatants of splenocytes and the serum level of IL-17A in mice were detected by ELISA. The intracellular cytokines were measured by flow cytometric analysis. The protein expression was measured using western blot. Results: This study show that the presence of JQ1 decreased the product and mRNA expression of IL-17A, but not IFNγ and TNFα, in anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs) from treatment-naive patients with early RA. The percentages of IL-17A-expressing CD4+ T cells were also reduced by JQ1 in stimulated PBMCs. JQ1 also inhibited the expression of the transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and T-bet. Furthermore, JQ1 inhibited hypoxia-inducible factor-1α (HIF-1α) expression, but did not affect activity of mammalian target of rapamycin complex 1 (mTORC1). HIF-1α inhibitor reduced percentage of IL-17A- expressing CD4+ T cells. Conclusions: This study indicated that the epigenetic readers BET bromodomain might contribute to regulating HIF-1α-mediated IL-17 expression in RA. BET bromodomain inhibition might be a novel therapeutic approach for RA.
| Published in | International Journal of Immunology (Volume 6, Issue 4) |
| DOI | 10.11648/j.iji.20180604.11 |
| Page(s) | 48-57 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2019. Published by Science Publishing Group |
Bromodomain and Extra-Terminal Domain, Th17, Rheumatoid Arthritis, HIF-1α
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APA Style
Youjun Xiao, Maohua Shi, Jingnan Wang, Ruiru Li, Qian Qiu, et al. (2019). BET Bromodomain Inhibition Suppresses HIF-1α-Mediated IL-17 Expression in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis. International Journal of Immunology, 6(4), 48-57. https://doi.org/10.11648/j.iji.20180604.11
ACS Style
Youjun Xiao; Maohua Shi; Jingnan Wang; Ruiru Li; Qian Qiu, et al. BET Bromodomain Inhibition Suppresses HIF-1α-Mediated IL-17 Expression in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis. Int. J. Immunol. 2019, 6(4), 48-57. doi: 10.11648/j.iji.20180604.11
AMA Style
Youjun Xiao, Maohua Shi, Jingnan Wang, Ruiru Li, Qian Qiu, et al. BET Bromodomain Inhibition Suppresses HIF-1α-Mediated IL-17 Expression in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis. Int J Immunol. 2019;6(4):48-57. doi: 10.11648/j.iji.20180604.11
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Download@article{10.11648/j.iji.20180604.11,
author = {Youjun Xiao and Maohua Shi and Jingnan Wang and Ruiru Li and Qian Qiu and Minxi Lao and Shan Zeng and Cuicui Wang and Siqi Xu and Yaoyao Zou and Liuqin Liang and Hanshi Xu},
title = {BET Bromodomain Inhibition Suppresses HIF-1α-Mediated IL-17 Expression in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis},
journal = {International Journal of Immunology},
volume = {6},
number = {4},
pages = {48-57},
doi = {10.11648/j.iji.20180604.11},
url = {https://doi.org/10.11648/j.iji.20180604.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20180604.11},
abstract = {Objectives: The purpose of this study was to explore the potential of the bromodomain and extra-terminal domain (BET) bromodomain to regulate IL-17 expression in peripheral blood from patients with rheumatoid arthritis (RA) and its underlying mechanisms. Methods: The level of IL-17A, TNFα and IFNγ in PBMCs from patients with RA was evaluated by a cytometric bead array. The IL-17A and IFNγ production in the supernatants of splenocytes and the serum level of IL-17A in mice were detected by ELISA. The intracellular cytokines were measured by flow cytometric analysis. The protein expression was measured using western blot. Results: This study show that the presence of JQ1 decreased the product and mRNA expression of IL-17A, but not IFNγ and TNFα, in anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs) from treatment-naive patients with early RA. The percentages of IL-17A-expressing CD4+ T cells were also reduced by JQ1 in stimulated PBMCs. JQ1 also inhibited the expression of the transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and T-bet. Furthermore, JQ1 inhibited hypoxia-inducible factor-1α (HIF-1α) expression, but did not affect activity of mammalian target of rapamycin complex 1 (mTORC1). HIF-1α inhibitor reduced percentage of IL-17A- expressing CD4+ T cells. Conclusions: This study indicated that the epigenetic readers BET bromodomain might contribute to regulating HIF-1α-mediated IL-17 expression in RA. BET bromodomain inhibition might be a novel therapeutic approach for RA.},
year = {2019}
}
TY - JOUR T1 - BET Bromodomain Inhibition Suppresses HIF-1α-Mediated IL-17 Expression in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis AU - Youjun Xiao AU - Maohua Shi AU - Jingnan Wang AU - Ruiru Li AU - Qian Qiu AU - Minxi Lao AU - Shan Zeng AU - Cuicui Wang AU - Siqi Xu AU - Yaoyao Zou AU - Liuqin Liang AU - Hanshi Xu Y1 - 2019/01/02 PY - 2019 N1 - https://doi.org/10.11648/j.iji.20180604.11 DO - 10.11648/j.iji.20180604.11 T2 - International Journal of Immunology JF - International Journal of Immunology JO - International Journal of Immunology SP - 48 EP - 57 PB - Science Publishing Group SN - 2329-1753 UR - https://doi.org/10.11648/j.iji.20180604.11 AB - Objectives: The purpose of this study was to explore the potential of the bromodomain and extra-terminal domain (BET) bromodomain to regulate IL-17 expression in peripheral blood from patients with rheumatoid arthritis (RA) and its underlying mechanisms. Methods: The level of IL-17A, TNFα and IFNγ in PBMCs from patients with RA was evaluated by a cytometric bead array. The IL-17A and IFNγ production in the supernatants of splenocytes and the serum level of IL-17A in mice were detected by ELISA. The intracellular cytokines were measured by flow cytometric analysis. The protein expression was measured using western blot. Results: This study show that the presence of JQ1 decreased the product and mRNA expression of IL-17A, but not IFNγ and TNFα, in anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs) from treatment-naive patients with early RA. The percentages of IL-17A-expressing CD4+ T cells were also reduced by JQ1 in stimulated PBMCs. JQ1 also inhibited the expression of the transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and T-bet. Furthermore, JQ1 inhibited hypoxia-inducible factor-1α (HIF-1α) expression, but did not affect activity of mammalian target of rapamycin complex 1 (mTORC1). HIF-1α inhibitor reduced percentage of IL-17A- expressing CD4+ T cells. Conclusions: This study indicated that the epigenetic readers BET bromodomain might contribute to regulating HIF-1α-mediated IL-17 expression in RA. BET bromodomain inhibition might be a novel therapeutic approach for RA. VL - 6 IS - 4 ER -
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