Immunosuppressive activity of pogostone on T cells: Blocking proliferation via S phase arrest
Immunosuppressive activity of pogostone on T cells: Blocking proliferation via S phase arrest
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DOI：
10.1016/j.intimp.2015.04.019
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发表时间：
2015-06-01
影响因子：
5.6
通讯作者：
Lai, Xiao-Ping
中科院分区：
文献类型：
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作者：
Su, Ji-Yan;Luo, Xia;Lai, Xiao-Ping
广藿香酮（Pogostone，PO）是广藿香（Pogostemon cablin（布兰科）Benth）挥发油的主要化学成分之一。在本研究中，PO对T细胞反应性的影响进行了研究，以探索其在免疫抑制中的潜力，通过刀豆球蛋白A（ConA）刺激模型，使用从C57 BL/6小鼠分离的脾细胞。通过MTS测定评价PO对正常脾细胞的细胞毒性。流式细胞仪分析细胞凋亡、增殖和细胞周期特征。流式细胞术检测细胞周期蛋白和细胞周期蛋白依赖性激酶（CDKs）的相关表达。采用流式细胞仪珠粒分析（CBA）进行炎性细胞因子分析。采用T细胞介导的迟发型过敏反应（DTH）模型评价PO的免疫抑制作用。在PO处理下，既没有观察到正常脾细胞的活力降低，也没有观察到ConA刺激的脾细胞的凋亡。同时，PO能显著降低ConA刺激的T细胞总数，阻断ConA诱导的T细胞增殖，抑制IFN-γ和IL-10的产生。PO对T细胞增殖的抑制作用可能与其下调cyclin E、cyclin B和CDK 1的表达及随后的S期阻滞有关。此外，PO还可通过减轻DNCB诱导的耳肿胀和炎症浸润来抑制DTH反应。总之，PO通过直接阻断T细胞增殖以及改变炎性细胞因子谱而表现出免疫抑制特性，这表明PO可能具有治疗自身免疫性疾病和其他基于免疫的疾病的临床意义。(C)2015 Elsevier B. V.版权所有。
Pogostone (PO) is one of the major chemical constituents of the essential oil of Pogostemon cablin (Blanco) Benth. In the present study, the effect of PO on T cell responsiveness was investigated to explore its potential in immunosuppression by a Concanavalin A (ConA)-stimulation model using splenocytes isolated from C57BL/6 mice. Cytotoxicity by PO on normal splenocytes was evaluated by MTS assays. Characteristics of apoptosis, proliferation, and cell cycle were analyzed by flow cytometry. Related expressions of cyclins and cyclin-dependent kinases (CDKs) were also determined by flow cytometry. Inflammatory cytokine profiling was performed emplying cytometric beads assays (CBA). Moreover, the T cell-mediated delayed Type hepersensity (DTH) model was applied to evaluate the immunosuppressive activity of PO. Neither viability reduction in normal splenocytes nor apoptosis in ConA-stimulated splenocytes was observed under PO treatments. Meanwhile, PO remarkably reduced the total population of ConA-stimulated T cell, blocked T cell proliferation induced by Con A, and inhibited the production of IFN-gamma and IL-10. This blockade of stimulated T cell proliferation by PO was likely attributed to down-regulation of cyclin E, cyclin B and CDK1 and the subsequent S-phase arrest Additionally, PO could inhibit the DTH reaction by alleviating ear swelling and inflammatory infiltrations in the DNCB-challenged ear. Taken together, PO exhibited an immunosuppressive property by directly blocking T cell proliferation as well as altering inflammatory cytokine profile, suggesting that PO may have clinical implications for treating autoimmune diseases and other immune-based disorders. (C) 2015 Elsevier B.V. All rights reserved.