Clematichinenoside AR induces immunosuppression involving Treg cells in Peyer's patches of rats with adjuvant induced arthritis
Clematichinenoside AR induces immunosuppression involving Treg cells in Peyer's patches of rats with adjuvant induced arthritis
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DOI：
10.1016/j.jep.2014.07.028
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发表时间：
2014-09-11
影响因子：
5.4
通讯作者：
Li, Yun-Man
中科院分区：
文献类型：
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作者：
Xiong, Ying;Ma, Yan;Li, Yun-Man
民族药理学相关性：威灵仙皂苷（Clematichinenoside AR，AR）是从传统中药威灵仙（Clematidis Radix et Rhizoma）中提取的一种三萜皂苷类化合物。为进一步探讨AR治疗RA的作用机制，我们在佐剂性关节炎（AIA）大鼠模型中研究AR的免疫调节作用是否与Peyer集合淋巴结（Peyer's patches，PPs）中Treg介导的抑制有关。材料与方法：免疫后第18天至第31天每天口服AR（8，16，32 mg/kg）。通过大鼠足跖肿胀和组织病理学检查评价AR对AIA大鼠的影响。流式细胞术检测CD 4（+）CD 25（+）Foxp 3（+）调节性T细胞的数量。通过ELISA测量IL-10、TGF-β（1）、IL-17 A和TNF-α的水平。结果：AR治疗可显著减轻ALA大鼠足肿胀，组织病理学分析证实AR治疗可抑制已建立的关节炎的严重程度。AR处理上调PP淋巴细胞中CD 4 + T细胞中CD 4（+）CD 25（+）Foxp 3（+）Treg细胞的百分比，并增加ConA激活的PP淋巴细胞分泌的IL-10和TGF-β（1）水平，而降低IL-17 A和TNE-α的水平。CD 4（+）CD 25（+）Foxp 3（+）Treg细胞百分比和血清细胞因子水平变化趋势相似。结论：AR对AIA的发生发展具有保护作用，其机制可能是通过增强PP中的CD 4（+）CD 25（+）Foxp 3（+）Treg细胞诱导免疫抑制，调节Treg细胞与Th 17细胞的平衡。这些发现可能有助于开发AR作为治疗RA的有效免疫抑制剂。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Clematichinenoside AR (AR) has been defined as a major active ingredient of triterpenoid saponins extracted from Clematidis Radix et Rhizoma, which is a traditional Chinese herbal medicine that has long been used in the treatment of rheumatoid arthritis (RA). To further explore the mechanism of AR in the treatment of RA, we investigated whether its immunomodulatory effects are related to Treg-mediated suppression derived from Peyer's patches (PPs) in adjuvant induced arthritis (AIA) rat model.Materials and methods: AR (8, 16, 32 mg/kg) was orally administered daily from Day 18 to Day 31 after immunization. The effect of AR on AIA rats was evaluated by hind paw swelling and histopathological examination. Percentages of CD4(+)CD25(+)Foxp3(+) T regulatory cells were determined by flow cytometry. Levels of IL-10, TGF-beta(1), IL-17A and TNF-alpha were measured by ELISA. Expressions of Foxp3 and ROR gamma in synovium were detected using immunohistochemical analysis.Results: AR treatment significantly reduced paw swelling of ALA rats, and histopathological analysis confirmed it could suppress severity of established arthritis. AR treatment upregulated the percentages of CD4(+)CD25(+)Foxp3(+) Treg cells among CD4+ T cells in PPs lymphocytes, and increased the levels of IL-10 and TGF-beta(1) secreted from ConA-activated PPs lymphocytes, whereas decreased the levels of IL-17 A and TNE-alpha. Similar tendency of circulating CD4(+)CD25(+)Foxp3(+) Treg cells percentages and serum cytokine levels were observed. Moreover, AR decreased the expression levels of Foxp3 and ROR gamma in joint synovial membrane.Conclusions: In conclusion, these results suggested AR has a potent protective effect on the progression of AIA, probably by augmenting CD4(+)CD25(+)Foxp3(+) Treg cells in PPs to induce immunosuppression, and modulating the balance between Treg cells and Th17 cells systemically. These findings may help to develop AR as a potent immunosuppressive agent for the treatment of RA. (C) 2014 Elsevier Ireland Ltd. All rights reserved.