Apigenin, a potent suppressor of dendritic cell maturation and migration, protects against collagen-induced arthritis.
Apigenin, a potent suppressor of dendritic cell maturation and migration, protects against collagen-induced arthritis.
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DOI：
10.1111/jcmm.12717
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发表时间：
2016-01
影响因子：
5.3
通讯作者：
Sun E
中科院分区：
文献类型：
--
作者：
Li X;Han Y;Zhou Q;Jie H;He Y;Han J;He J;Jiang Y;Sun E
本研究旨在探讨芹菜素(API)是否通过调节树突状细胞功能来抑制关节炎的发展。体外用脂多糖(LPS)刺激骨髓来源的树突状细胞(BMDCs)，用API处理24小时，观察DC的表型表达、细胞因子分泌、吞噬功能和趋化功能。在体内观察API对胶原诱导性关节炎(CIA)的影响，并分析API处理CIA小鼠的淋巴结树突状细胞(LNS)的表型和亚群。在体外，API有效地抑制了脂多糖刺激的BMDCs的表型成熟和功能成熟，同时保持了吞噬能力。此外，API抑制内毒素刺激的BMDCs的趋化反应，这可能与其抑制趋化因子受体4(CXCR4)有关。在体内，API治疗延缓了CIA小鼠关节炎的发生，减轻了关节炎的严重程度，并减少了CIA小鼠血清和LN细胞上清液中促炎细胞因子的分泌。与体外研究结果相似，API处理的小鼠表现出DC上共刺激分子和主要组织相容性复合体II的表达减少。此外，API可显著下调LNS中朗格汉斯细胞的数量，但不影响浆细胞样树突状细胞(PDCs)的数量，这可能与API抑制外周血树突状细胞表面CXCR4的表达有关。这些结果为揭示API治疗关节炎的作用机制提供了新的思路，提示API抑制DC的成熟和迁移可能是其免疫抑制作用的机制之一。
This study aimed to investigate whether apigenin (API) suppresses arthritis development through the modulation of dendritic cell functions. Bone marrow‐derived dendritic cells (BMDCs) were stimulated in vitro with lipopolysaccharide (LPS) and treated with API for 24 hrs; DC functions, including phenotype expressions, cytokine secretion, phagocytosis and chemotaxis, were then investigated. The effects of API on collagen‐induced arthritis (CIA) were examined in vivo, and purified DCs from the lymph nodes (LNs) of API‐treated CIA mice were analysed for phenotypes and subsets. In in vitro, API efficiently restrained the phenotypic and functional maturation of LPS‐stimulated BMDCs while maintaining phagocytotic capabilities. Moreover, API inhibited the chemotactic responses of LPS‐stimulated BMDCs, which may be related to the depressive effect on chemokine receptor 4 (CXCR4). In in vivo, API treatment delayed the onset and reduced the severity of arthritis in CIA mice, and diminished secretion of pro‐inflammatory cytokines in the serum and supernatants from the LN cells of the CIA mice. Similar to the in vitro findings, the API‐treated mice exhibited reduced expression of co‐stimulatory molecules and major histocompatibility complex II on DCs. Furthermore, API treatment strongly down‐regulated the number of Langerhans cells, but not plasmacytoid DCs (pDCs) in LNs, which may be related to the depressive effect of API on the expression of CXCR4 on DCs of peripheral blood. These data provide new insight into the mechanism of action of API on arthritis and indicate that the inhibition of maturation and migration of DCs by API may contribute to its immunosuppressive effects.