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杠柳苷A通过调节Th17/Treg细胞平衡改善小鼠II型胶原诱导的关节炎。

Periplocoside A ameliorated type II collagen-induced arthritis in mice via regulation of the balance of Th17/Treg cells.

作者信息

Yang Yang, Hu Xudong, Cheng Lei, Tang Wei, Zhao Weimin, Yang Yifu, Zuo Jianping

机构信息

Laboratory of Immunology and Virology, Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, China.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.

出版信息

Int Immunopharmacol. 2017 Mar;44:43-52. doi: 10.1016/j.intimp.2016.12.013. Epub 2017 Jan 7.

Abstract

Periplocoside A (PSA) has been extracted from the Chinese herbal medicine Periploca sepium Bge to treat rheumatoid arthritis (RA) via immune regulation. We previously found that PSA exhibits immunosuppressive activity both in vitro and in vivo. Balanced regulation of helper T 17 (Th17)/regulatory T (Treg) cells is the current therapeutic direction for the treatment of RA. The present study investigated the mechanism of PSA in treating collagen-induced arthritis (CIA). The therapeutic effects and potential pharmacological mechanisms of PSA were specifically clarified by examining its effects on CIA in DBA/1 mice. PSA administration significantly relieved the severity of the arthritis, and preventive administration of PSA reduced the incidence of arthritis in the mice with CIA and relieved joint damage in terms of morphology. PSA was also able to reduce the levels of anti-collagen II (CII) antibodies and pro-inflammatory cytokines in the serum. As a result, the proportion of Th17 cells decreased, and the proportion of Treg cells increased. A follow-up study of the ex vivo immunological reactions induced by a specific antigen found that PSA suppressed lymphocyte proliferation, inhibited the differentiation and reactivity of Th17 cells, and promoted the proportion of Treg cells among helper T cells. PSA also exhibited pharmacological effect in regulating the balance between Th17 and Treg cells in CIA through relevant signalling pathways. Thus, PSA played a specific role in CIA treatment. In particular, our results suggest that the therapeutic effects of PSA on RA are partially realized via the regulation of the balance of Th17/Treg cells.

摘要

杠柳苷A(PSA)已从中药杠柳中提取出来,通过免疫调节来治疗类风湿性关节炎(RA)。我们之前发现PSA在体外和体内均表现出免疫抑制活性。辅助性T细胞17(Th17)/调节性T(Treg)细胞的平衡调节是目前治疗RA的治疗方向。本研究探讨了PSA治疗胶原诱导性关节炎(CIA)的机制。通过检测PSA对DBA/1小鼠CIA的影响,具体阐明了PSA的治疗效果和潜在的药理机制。给予PSA可显著减轻关节炎的严重程度,预防性给予PSA可降低CIA小鼠的关节炎发病率,并在形态学上减轻关节损伤。PSA还能够降低血清中抗II型胶原(CII)抗体和促炎细胞因子的水平。结果,Th17细胞比例降低,Treg细胞比例增加。对特定抗原诱导的体外免疫反应进行的后续研究发现,PSA抑制淋巴细胞增殖,抑制Th17细胞的分化和反应性,并促进辅助性T细胞中Treg细胞的比例。PSA还通过相关信号通路在调节CIA中Th17和Treg细胞之间的平衡方面表现出药理作用。因此,PSA在CIA治疗中发挥了特定作用。特别是,我们的结果表明,PSA对RA的治疗作用部分是通过调节Th17/Treg细胞平衡来实现的。

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