Huperzine A Inhibits CCL2 Production in Experimental Autoimmune Encephalomyelitis Mice and in Cultured Astrocyte
Huperzine A Inhibits CCL2 Production in Experimental Autoimmune Encephalomyelitis Mice and in Cultured Astrocyte
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石杉碱甲抑制实验性自身免疫性脑脊髓炎小鼠和培养星形胶质细胞中 CCL2 的产生
DOI：
10.1177/039463201302600320
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发表时间：
2013
影响因子：
3.5
通讯作者：
J. Wang
中科院分区：
文献类型：
--
作者：
G. Tian;X.Q. Zhu;Y. Chen;G. Wu;J. Wang
在实验性自身免疫性脑脊髓炎（EAE）的发病机制中，趋化因子和炎症细胞因子在中枢神经系统（CNS）中的积极作用已经明确。我们实验室最近的研究报告称，石杉碱甲 (HupA) 可以通过抑制脊髓炎症、脱髓鞘和轴突损伤以及脑脊髓炎 T 细胞增殖来减轻 EAE 的疾病进程。在本研究中，评估了低剂量 HupA 对 EAE 中 CCL2、TNF-α、IL-6 和 IL-1β 表达的影响。在体外培养的星形胶质细胞中研究了 HupA 对脂多糖 (LPS) 诱导的炎症分子分泌的影响。在MOG35-55诱导的EAE小鼠中，腹腔注射HupA（0.1 mg/kg·d−1）显着抑制脊髓中CCL2、IL-6、TNF-α和IL-1β的表达。 HupA 还抑制 LPS 诱导的 CCL2 产生，但对原代培养的星形胶质细胞中的促炎细胞因子影响很小。 HupA 对 CCL2 的抑制作用依赖于 PPARγ，且不依赖于尼古丁受体。 HupA 处理的星形胶质细胞的条件培养基可减少体外 PBMC 迁移。总的来说，这些结果表明 HupA 可以通过抑制星形胶质细胞中 CCL2 的产生来改善 EAE，从而减少脊髓中的炎症细胞浸润。 HupA可能对治疗多发性硬化症和其他神经炎症性疾病具有潜在的治疗价值。
The active role of chemokines and inflammatory cytokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. Recent studies from our laboratory reported that Huperzine A (HupA) can attenuate the disease process in EAE by the inhibition of inflammation, demyelination, and axonal injury in the spinal cord as well as encephalomyelitic T-cell proliferation. In this study, the effects of low dose HupA on CCL2, TNF-α, IL-6, and IL-1β expression were evaluated in EAE. The effect of HupA on lipopolysachharide (LPS)-induced inflammatory molecule secretion was investigated in cultured-astrocytes in vitro. In MOG35-55-induced EAE mice, intraperitoneal injections of HupA (0.1 mg/kg·d−1) significantly suppressed the expression of CCL2, IL-6, TNF-alpha, and IL-1beta in the spinal cord. HupA also repressed LPS-induced CCL2 production, but with little influence on pro-inflammatory cytokines in primary cultured astrocytes. The inhibition effect of HupA on CCL2 is PPARγ-dependent and nicotine receptor-independent. Conditioned culture media from HupA-treated astrocyte decreased PBMC migration in vitro. Collectively, these results suggest that HupA can ameliorate EAE by inhibiting CCL2 production in astrocyte, which may consequently decrease inflammatory cell infiltration in the spinal cord. HupA may have a potential therapeutic value for the treatment of MS and other neuroinflammatory diseases.
影响因子：
15.9
作者：
Wilson, Emma H.;Weninger, Wolfgang;Hunter, Christopher A.
通讯作者：
Hunter, Christopher A.