Immunomodulatory activity of polysaccharides isolated from Clerodendrum splendens: beneficial effects in experimental autoimmune encephalomyelitis.
Immunomodulatory activity of polysaccharides isolated from Clerodendrum splendens: beneficial effects in experimental autoimmune encephalomyelitis.
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DOI：
10.1186/1472-6882-13-149
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发表时间：
2013-06-28
影响因子：
--
通讯作者：
Quinn MT
中科院分区：
文献类型：
--
作者：
Kouakou K;Schepetkin IA;Jun S;Kirpotina LN;Yapi A;Khramova DS;Pascual DW;Ovodov YS;Jutila MA;Quinn MT
几个世纪以来，Clerodendrum的叶子提取物一直用于治疗热带非洲的各种医学问题。然而，鲜为人知的是，高分子量的活性成分赋予这些提取物的治疗特性。采用离子交换和分子排阻色谱法对大青叶多糖进行分离纯化。分子量测定，糖分析，甲酯化度，和其他化学表征的馏分进行。通过测定其诱导单核细胞/巨噬细胞一氧化氮（NO）、细胞因子产生和丝裂原活化蛋白激酶（MAPK）磷酸化的能力来评价各组分的免疫调节活性。在C57 BL/6小鼠中诱导实验性自身免疫性脑脊髓炎（EAE），并在用腹膜内（i. p.）注射最具活性的多糖组分。收集淋巴结（LN）和脾脏，测定用髓鞘少突胶质细胞糖蛋白肽攻击的LN细胞和脾细胞上清液中细胞因子的水平。含有II型阿拉伯半乳聚糖的馏分具有强效免疫调节活性。具体而言，高分子量亚组分CSP-AU 1（平均值为38.5 kDa）诱导人外周血单核细胞（PBMC）和单核细胞/巨噬细胞产生NO和细胞因子[白细胞介素（IL）-1α、-1β、-6、-10、肿瘤坏死因子（TNF;先前指定为TNF-α）和粒细胞巨噬细胞集落刺激因子（GM-CSF）]。Toll样受体4（TLR 4）拮抗剂LPS-RS阻止CSP-AU 1诱导的TNF分泌，表明TLR 4信号传导的作用。用CSP-AU 1处理还诱导人PBMC中许多MAPK的磷酸化和激活AP-1/NF-κB。用CSP-AU 1和CSP-NU 1对小鼠进行体内处理导致血清IL-6、IL-10、TNF、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白（MIP）-1α/CCL 3和MIP-1β/CCL 4升高。CSP-AU 1处理EAE小鼠（50 mg/kg，i. p.，每天，13天）导致该多发性硬化症实验模型中疾病严重程度显著降低。IL-13、TNF、干扰素（IFN）-γ、IL-17和GM-CSF的水平也显著降低，而转化生长因子（TGF）-β在CSP-AU 1处理的EAE小鼠的LN细胞中升高。多糖CSP-AU 1是一种有效的天然先天性免疫调节剂，在体外具有广谱激动剂活性，在体内长期给药后具有免疫抑制特性。
Extracts of leaves from Clerodendrum have been used for centuries to treat a variety of medicinal problems in tropical Africa. However, little is known about the high-molecular weight active components conferring therapeutic properties to these extracts. Polysaccharides from the leaves of Clerodendrum splendens were extracted and fractionated by ion exchange and size-exclusion chromatography. Molecular weight determination, sugar analysis, degree of methyl esterification, and other chemical characterization of the fractions were performed. Immunomodulatory activity of the fractions was evaluated by determining their ability to induce monocyte/macrophage nitric oxide (NO), cytokine production, and mitogen-activated protein kinase (MAPK) phosphorylation. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice, and severity of EAE was monitored in mice treated with intraperitoneal (i.p.) injections of the most active polysaccharide fraction. Lymph nodes (LN) and spleen were harvested, and levels of cytokines in supernatants from LN cells and splenocytes challenged with myelin oligodendrocyte glycoprotein peptide were determined. Fractions containing type II arabinogalactan had potent immunomodulatory activity. Specifically, the high-molecular weight sub-fraction CSP-AU1 (average of 38.5 kDa) induced NO and cytokine [interleukin (IL)-1α, -1β, -6, -10, tumor necrosis factor (TNF; designated previously as TNF-α), and granulocyte macrophage-colony stimulating factor (GM-CSF)] production by human peripheral blood mononuclear cells (PBMCs) and monocyte/macrophages. CSP-AU1-induced secretion of TNF was prevented by Toll-like receptor 4 (TLR4) antagonist LPS-RS, indicating a role for TLR4 signaling. Treatment with CSP-AU1 also induced phosphorylation of a number of MAPKs in human PBMC and activated AP-1/NF-κB. In vivo treatment of mice with CSP-AU1 and CSP-NU1 resulted in increased serum IL-6, IL-10, TNF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α/CCL3, and MIP-1β/CCL4. CSP-AU1 treatment of mice with EAE (50 mg/kg, i.p., daily, 13 days) resulted in significantly reduced disease severity in this experimental model of multiple sclerosis. Levels of IL-13, TNF, interferon (IFN)-γ, IL-17, and GM-CSF were also significantly decreased, whereas transforming growth factor (TGF)-β was increased in LN cells from CSP-AU1-treated EAE mice. Polysaccharide CSP-AU1 is a potent natural innate immunomodulator with a broad spectrum of agonist activity in vitro and immunosupressive properties after chronic administration in vivo.
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影响因子：
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作者：
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通讯作者：
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