Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production
Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production
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DOI：
10.1016/j.intimp.2009.01.025
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发表时间：
2009-05-01
影响因子：
5.6
通讯作者：
Takahara, Shiro
中科院分区：
文献类型：
--
作者：
Xie, Lin;Li, Xiao-Kang;Takahara, Shiro
实验性自身免疫性脑脊髓炎（Experimental autoimmune encephalomylitis，EAE）是多发性硬化（multiple sclerosis，MS）的一种动物模型，以前认为是由Th 1细胞介导的。然而，最近的一些研究提供了强有力的证据表明，产生IL-17的T辅助细胞在EAE的发病机制中起主导作用。姜黄素（1，7-双94-羟基3-甲氧基苯基）-1，6庚二烯-3，5-二酮）是一种从药用植物姜黄根茎中分离出的天然多酚植物化学物质。它被强烈地暗示为抗炎剂，但其作用的确切机制在很大程度上是未知的。在本研究中，我们研究了姜黄素对EAE的疗效和机制。用姜黄素治疗刘易斯大鼠显著降低了EAE的临床严重程度，并显著减少了脊髓中炎性细胞浸润的数量。MBP反应淋巴细胞的增殖也以姜黄素剂量依赖性方式减少。此外，通过定量逆转录聚合酶链反应（qRT-PCR）评估细胞因子谱的mRNA表达，揭示姜黄素处理组中IL-17、TGF-β、IL-6、IL-21、STAT 3和ROR γ t表达显著降低，并且STAT 3磷酸化也被抑制。这些结果表明姜黄素改善EAE在很大程度上是由于抑制Th 17细胞的分化和发育，依赖于下调IL-6、IL-21、ROR γ t信号的表达和抑制STAT 3-磷酸化，提示其在MS等Th 17细胞介导的炎症性疾病的治疗中是有用的。(C)2009爱思唯尔有限公司版权所有。
Experimental autoimmune encephalomylitis (EAE), an animal mode of multiple sclerosis (MS), was previously considered that be mediated by Th1 cells. However, a number of recent studies provided strong evidence that T helper cells that produce IL-17 play a dominant role in the pathogenesis of EAE. Curcumin (1,7-Bis 94-hydroxy3-methoxyphenyl)-1,6 heptadiene-3, 5-di-one) is a naturally occurring polyphenolic phytochemical isolated from the rhizome of the medicinal plant Curcuma longa. It has been strongly implicated as an anti-inflammatory agent, but the precise mechanisms of its action are largely unknown. In the present study, we have investigated the efficacy and mechanism of curcumin against EAE. The treatment of Lewis rats with curcumin significantly reduced the clinical severity of EAE, and had a dramatic reduction in the number of inflammatory cells infiltration in the spinal cord. The proliferation of the MBP-reaction lymphocyte also was reduced in a curcumin dose-dependent manner. Furthermore, the mRNA expression of the cytokine profiles was assessed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), revealing the dramatic decrease of IL-17, TGF-beta, IL-6, IL-21, STAT3, and ROR gamma t expression in curcumin-treated groups and STAT3-phosphorylation also was inhibited. These findings indicated that curcumin amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-21, ROR gamma t signaling and inhibition STAT3-phosphorylation, suggests it is useful in the treatment of MS and other Th17 cell-mediated inflammatory diseases. (C) 2009 Elsevier B.V. All rights reserved.