GTS-21, an α7-nicotinic acetylcholine receptor agonist, modulates Th1 differentiation in CD4+ T cells from patients with rheumatoid arthritis

被引:20
作者
Wu, Shiyao [1 ]
Zhao, Hongjun [1 ]
Luo, Hui [1 ]
Xiao, Xianzhong [2 ]
Zhang, Huali [2 ]
Li, Tong [1 ]
Zuo, Xiaoxia [1 ]
机构
[1] Cent S Univ, Xiangya Hosp, Dept Rheumatol, Changsha 410008, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Sch Med, Dept Pathophysiol, Changsha 410008, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
GTS-21; Th1; cells; TBX21; alpha; 7nAchR; rheumatoid arthritis; INTERFERON-GAMMA; EXPRESSION; INFLAMMATION; LYMPHOCYTES; SURVIVAL; SEPSIS;
D O I
10.3892/etm.2014.1754
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
GTS-21 (also known as DMBX-anabaseine), a selective alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) agonist, has previously been found to inhibit the inflammation associated with rheumatoid arthritis (RA). RA is an autoimmune disease, where an abnormal immune system plays a critical role in the occurrence and development of synovium inflammation and bone damage. However, prior to this study, the immunological mechanism by which GTS-21 protects against RA had not been elucidated. In the present study, the effects of GTS-21 on T helper 1 (Th1) cells, which have an important role in the inflammation associated with RA, were investigated. Peripheral blood mononuclear cells (PBMCs) and cluster of differentiation (CD)4(+) T cells were separated from patients with RA, and the effects of GTS-21 on PBMCs stimulated with anti-CD3/-CD28 antibodies and CD4(+) T cells were investigated in the context of Th1-cell differentiation. ELISA was used to analyze interferon.(IFN)-gamma expression and flow cytometric analysis was used to detect the percentage of IFN-gamma(+) CD3(+)CD8(-) T cells. In addition, western blotting was employed to detect the levels of the T-box transcription factor TBX21, which is a Th1 cell-specific transcription factor. The present study showed that GTS-21 reduced IFN-gamma production in PBMCs from patients with RA. Under conditions of Th1-cell differentiation, GTS-21 reduced the percentage of IFN gamma(+)CD3(+)CD8(-) T cells and IFN-gamma production in the culture supernatant and also inhibited the expression of the Th1 cell-specific transcription factor TBX21. The effects of GTS-21 were blocked by the alpha 7nAchR antagonist a-bungarotoxin, which increased the expression of IFN-gamma and TBX21. This study demonstrated that GTS-21 is able to inhibit RA Th1-cell differentiation through activation of the alpha 7nAchR.
引用
收藏
页码:557 / 562
页数:6
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