BET Bromodomain Inhibition Suppresses HIF-1α-Mediated IL-17 Expression in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis
International Journal of Immunology
Volume 6, Issue 4, December 2018, Pages: 48-57
Received: Nov. 11, 2018;
Accepted: Dec. 7, 2018;
Published: Jan. 2, 2019
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Youjun Xiao, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Maohua Shi, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Jingnan Wang, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Ruiru Li, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Qian Qiu, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Minxi Lao, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Shan Zeng, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Cuicui Wang, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Siqi Xu, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Yaoyao Zou, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Liuqin Liang, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Hanshi Xu, Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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.
BET Bromodomain Inhibition Suppresses HIF-1α-Mediated IL-17 Expression in Peripheral Blood Mononuclear Cells from Patients with Rheumatoid Arthritis, International Journal of Immunology.
Vol. 6, No. 4,
2018, pp. 48-57.
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