Anti-inflammatory effects of plumbagin are mediated by inhibition of NF-kappaB activation in lymphocytes
Anti-inflammatory effects of plumbagin are mediated by inhibition of NF-kappaB activation in lymphocytes
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DOI：
10.1016/j.intimp.2009.03.022
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发表时间：
2009-07-01
影响因子：
5.6
通讯作者：
Poduval, T. B.
中科院分区：
文献类型：
--
作者：
Checker, Rahul;Sharma, Deepak;Poduval, T. B.
白花丹素（5-羟基-2-甲基-1，4-萘醌）是从白花丹（Plumbago zeylanica）根中分离得到的一种醌类化合物，近年来发现它能抑制肿瘤细胞NF-κ B B的活化。NF-κ B B是一种普遍存在的转录因子，在调节白细胞的多种过程中起着重要作用，如细胞增殖、免疫调节基因的表达以及先天性和适应性免疫应答过程中的细胞凋亡。因此，白花丹素可能会影响白细胞参与各种免疫反应的生物学功能。本报告描述了新的免疫调节作用的白花丹素。白花丹素通过阻断细胞周期进程来抑制T细胞对多克隆丝裂原伴刀豆球蛋白A（Con A）的增殖反应。它还分别抑制活化T细胞中早期和晚期活化标志物CD 69和CD 25的表达。在这些免疫抑制剂量（高达5 μ M），白花丹素没有降低淋巴细胞的活力。此外，白花丹素对T细胞增殖的抑制伴随着Con A诱导的IL-2、IL-4、IL-6和IFN-γ细胞因子水平的降低。在体内观察到白花丹素对细胞因子水平的类似免疫抑制作用。为了表征白花丹素的抑制作用机制，在淋巴细胞中研究了有丝分裂原诱导的I κ B-α降解和NF-κ B的核转位。白花丹素完全抑制Con A诱导的I κ B-α降解和NF-κ B活化。此外，白花丹素防止小鼠中移植物抗宿主病诱导的死亡。据我们所知，这是第一份报告显示白花丹素在淋巴细胞中通过调节NF-κ B活化的免疫调节作用。(C)2009爱思唯尔有限公司版权所有。
Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a quinone isolated from the roots of Plumbago zeylanica was recently reported to suppress the activation of NF-kappa B in tumor cells. NF-kappa B, a ubiquitous transcription factor, plays a central role in regulating diverse processes in leukocytes like cellular proliferation, expression of immunoregulatory genes and apoptosis during innate and adaptive immune responses. Consequently, plumbagin might affect the biological functions of leukocytes participating in various immune responses. The present report describes novel immunomodulatory effects of plumbagin. Plumbagin inhibited T cell proliferation in response to polyclonal mitogen Concanavalin A (Con A) by blocking cell cycle progression. It also suppressed expression of early and late activation markers CD69 and CD25 respectively, in activated T cells. At these immunosuppressive doses (up to 5 mu M), plumbagin did not reduce the viability of lymphocytes. Further, the inhibition of T cell proliferation by plumbagin was accompanied by a decrease in the levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines. Similar immunosuppressive effects of plumbagin on cytokine levels were seen in vivo. To characterize the mechanism of inhibitory action of plumbagin, the mitogen induced I kappa B-alpha degradation and nuclear translocation of NF-kappa B was studied in lymphocytes. Plumbagin completely inhibited Con A induced I kappa B-alpha degradation and NF-kappa B activation. Further, plumbagin prevented Graft Versus Host Disease-induced mortality in mice. To our knowledge this is the first report showing the immunomodulatory effects of plumbagin in lymphocytes via modulation of NF-kappa B activation. (C) 2009 Elsevier B.V. All rights reserved.