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韦氏马尾藻多糖通过抑制组蛋白乙酰化抑制 PCV2 诱导的小鼠炎症。

Inhibitory effect of polysaccharide of Sargassum weizhouense on PCV2 induced inflammation in mice by suppressing histone acetylation.

机构信息

College of Animal Science and Technology, Guangxi University, Nanning, Guangxi 530005, China.

College of Animal Science and Technology, Guangxi University, Nanning, Guangxi 530005, China; Guangxi Academy of Fishery Science, Nanning, Guangxi, 530021, China.

出版信息

Biomed Pharmacother. 2019 Apr;112:108741. doi: 10.1016/j.biopha.2019.108741. Epub 2019 Mar 2.

Abstract

Seaweeds are excellent source of bioactive compounds and seaweed-derived polysaccharides have demonstrated an array of biological effects. Here, we investigated the effect of polysaccharide of Sargassum weizhouense (PSW) on the inflammatory response in porcine circovirus type 2 (PCV2) infected mice and the underlying mechanism was studied according to the histone acetylation. After PCV2 infection, the levels of TNF-α, IL-1β, IL-6, IL-8, IL-10, MCP-1, COX-1, COX-2 and HAT in both serum and spleen were significantly increased (P <0.05). The mRNA expression of TNF-α, IL-6, IL-10 and NF-κB p65 were elevated in PCV2 infected mice (P <0.05). The HDAC content in both serum and spleen as well the mRNA expression of HDAC1 were greatly decreased (P <0.05). PSW treatment dramatically inhibited the secretions of inflammatory cytokines and HATs, reduced mRNA expression of TNF-α, IL-6, IL-10 and NF-κB p65, but promoted HDAC secretion and mRNA expression of HDAC1 in PCV2-infected mice. The acetylation of both H3 and H4 was significantly up-regulated in PCV2-infected mice, and strongly inhibited by PSW treatment (P <0.01). These results suggested that PCV2 mediate the equilibrium between HATs and HDACs, alternate the histone acetylation and thus DNA packaging, and then activate the transcription of inflammatory cytokines. PSW could inhibit the histone acetylation and the production of inflammatory cytokines, showing excellent potentials in improving the resistance of host against PCV2 infection.

摘要

海藻是生物活性化合物的极好来源,并且已经证明海藻衍生的多糖具有多种生物学作用。在这里,我们研究了来自马尾藻的多糖(PSW)对感染猪圆环病毒 2 (PCV2)的小鼠炎症反应的影响,并根据组蛋白乙酰化研究了其潜在机制。在 PCV2 感染后,血清和脾脏中 TNF-α、IL-1β、IL-6、IL-8、IL-10、MCP-1、COX-1、COX-2 和 HAT 的水平均显着升高(P<0.05)。PCV2 感染小鼠的 TNF-α、IL-6、IL-10 和 NF-κB p65 的 mRNA 表达均升高(P<0.05)。血清和脾脏中的 HDAC 含量以及 HDAC1 的 mRNA 表达均大大降低(P<0.05)。PSW 处理可显着抑制炎症细胞因子和 HAT 的分泌,降低 TNF-α、IL-6、IL-10 和 NF-κB p65 的 mRNA 表达,但可促进 PCV2 感染小鼠的 HDAC 分泌和 HDAC1 的 mRNA 表达。PCV2 感染小鼠的 H3 和 H4 乙酰化均显着上调,并被 PSW 处理强烈抑制(P<0.01)。这些结果表明,PCV2 介导 HATs 和 HDACs 之间的平衡,改变组蛋白乙酰化和 DNA 包装,从而激活炎症细胞因子的转录。PSW 可抑制组蛋白乙酰化和炎症细胞因子的产生,显示出改善宿主对 PCV2 感染的抵抗力的巨大潜力。

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