Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease
Hyperforin down-regulates effector function of activated T lymphocytes and shows efficacy against Th1-triggered CNS inflammatory-demyelinating disease
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DOI：
10.1189/jlb.0707469
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发表时间：
2008-01-01
影响因子：
5.5
通讯作者：
Agostini, Carlo
中科院分区：
文献类型：
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作者：
Cabrelle, Anna;Dell'Aica, Isabella;Agostini, Carlo
贯叶连翘素（Hyp）是贯叶连翘（Hypericum perforatum）提取物中的一种活性化合物，因其抗抑郁活性而闻名。然而，已发现Hyp具有若干其他生物学特性，包括对肿瘤侵袭、血管生成和炎症的抑制作用。在这篇论文中，我们表明，用Hyp处理抑制IFN-γ的产生，下调T-box（T-bet; Th 1基因表达的标记）和上调加塔-3（Th 2的标记基因）对IL-2/PHA激活的T细胞。与此同时，我们发现活化T细胞上趋化因子受体CXCR 3表达的强烈下调。后一种效应和基质金属蛋白酶9表达的下调可能最终导致我们在体外观察到的活化淋巴细胞对趋化因子CXCL 10的迁移能力和基质穿越的抑制。因此，Hyp的效果进行了评估的实验性过敏性脑脊髓炎（EAE），一个经典的，Th 1介导的自身免疫性疾病的中枢神经系统的动物模型，我们观察到，Hyp减弱疾病症状的严重程度显着。总之，这些特性使Hyp有资格作为一种推定的治疗性分子，用于治疗由Th 1细胞维持的自身免疫性炎症性疾病，包括EAE。
Hyperforin (Hyp) is an active compound contained in the extract of Hypericum perforatum, well known for its antidepressant activity. However, Hyp has been found to possess several other biological properties, including inhibitory effects on tumor invasion, angiogenesis, and inflammation. In this paper, we show that treatment with Hyp inhibited IFN-gamma production, with down-regulation of T-box (T-bet; marker of Th1 gene expression) and up-regulation of GATA-3 (marker gene of Th2) on IL-2/PHA-activated T cells. In parallel, we showed a strong down-regulation of the chemokine receptor CXCR3 expression on activated T cells. The latter effect and the down-modulation of matrix metalloproteinase 9 expression may eventually lead to the inhibition of migratory capability and matrix traversal toward the chemoattractant CXCL10 by activated lymphocytes that we observed in vitro. The effect of Hyp was thus evaluated on an animal model of experimental allergic encephalomyelitis (EAE), a classic, Th1-mediated autoimmune disease of the CNS, and we observed that Hyp attenuates the severity of the disease symptoms significantly. Together, these properties qualify Hyp as a putative, therapeutic molecule for the treatment of autoimmune inflammatory disease sustained by Th1 cells, including EAE.