Effect of JQ1 on expression of autoimmune-related genes in CD4+T cells of systemic lupus erythematosus.
10.11817/j.issn.1672-7347.2018.07.002
- Author:
Xiaofei GAO
1
;
Keqin GAO
2
;
Jiali WU
1
;
Ming ZHAO
1
Author Information
1. Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Central South University,Changsha 410011, China.
2. Department of Pharmaceutics, Third Xiangya Hospital, Central South University, Changsha 410013, China.
- Publication Type:Journal Article
- MeSH:
Azepines;
pharmacology;
CD4 Lymphocyte Count;
CD4-Positive T-Lymphocytes;
cytology;
drug effects;
metabolism;
Cytokines;
analysis;
metabolism;
Flow Cytometry;
Humans;
Interferon-gamma;
metabolism;
Lupus Erythematosus, Systemic;
immunology;
metabolism;
Proteins;
antagonists & inhibitors;
RNA, Messenger;
metabolism;
Time Factors;
Transforming Growth Factor beta1;
Triazoles;
pharmacology
- From:
Journal of Central South University(Medical Sciences)
2018;43(7):704-710
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effect of bromodomain and extra-terminal (BET) protein inhibitor JQ1 on expression of autoimmune-related genes in CD4+T cells from patients with systemic lupus erythematosus (SLE).
Methods: Peripheral CD4+T cells were isolated by positive selection with CD4 microbeads. The percentage of CD4+T cells were detected by flow cytometry. CD4+T cells were treated by JQ1 at 100 nm/L for 6, 24, 48 h. The expression of T cell-related genes was measured by quantitative real-time PCR (qPCR). The secretion levels of cytokines in culture supernatant were measured by ELISA at 48 h.
Results: The percentage of CD4+T cells isolated by CD4 microbeads is 97.2%. Compared with the control group, the mRNA expression levels of IFNG, IL-17F, IL-21, CXCR5 and FOXP3 were down-regulated at 6, 24 and 48 h (P<0.05), and IL-17A mRNA level was decreased at 6 and 24 h (P<0.01); while IL-4 mRNA level was up-regulated at 24, 48 h (P<0.01), and TGF-β1 mRNA level was up-regulated at 6 and 48 h (P<0.05) in SLE CD4+T cells treated with JQ1. The secretion levels of IFN-γ and IL-21 in JQ1-treated group were decreased significantly (P<0.05), while the secretion levels of IL-4 and TGF-β were up-regulated compared with control group (P<0.05).
Conclusion: JQ1 can reverse the immune dysregulation and improve the immunity homeostasis in CD4+T cells from patients with SLE.
