College of Animal Science and Technology, Guangxi University, Nanning 530005, PR China.
Guangxi Beidouxing Animal Health Pharmaceutical Co., Ltd., Nanning 530002, PR China.
Int J Biol Macromol. 2017 Nov;104(Pt A):900-908. doi: 10.1016/j.ijbiomac.2017.06.102. Epub 2017 Jun 27.
In the present study, effect of Sophora subprosrate polysaccharide on PCV2 infection-induced inflammation and histone acetylation modification in swine alveolar macrophage 3D4/2 cells was described for the first time. The relationship between histone acetylation modifications and inflammation response was investigated. The results showed that PCV2 infection induced inflammation by promoting the secretion of TNF-α, IL-1β, IL-6 and IL-10 in 3D4/2 cells. The production of TNF-α, IL-1β and IL-6 and their mRNA expression levels markedly decreased while the level and mRNA expression of IL-10 were elevated when the cells were treated with Sophora subprosrate polysaccharide. The SSP also decreased the activity of HATs, histone H3 acetylation (Ac-H3) and histone H4 acetylation (Ac-H4), p65 phosphorylation (P-p65) in the cells infected with PCV2 while HDACs activity was down-regulated, which involved in the inhibitory effect of SSP on histone acetylation and NF-κB signaling pathways activation. Down-regulation of HAT1 mRNA expression and up-regulation of HDAC1 mRNA expression further support the inhibitory effect of SSP on histone acetylation. In conclusion, Sophora subprosrate polysaccharide antagonized inflammatory responses induced by PCV2, via mechanisms involved in histone acetylation and NF-κB signaling pathways.
本研究首次描述了苦参多糖对 PCV2 感染诱导的猪肺泡巨噬细胞 3D4/2 细胞炎症和组蛋白乙酰化修饰的影响,并探讨了组蛋白乙酰化修饰与炎症反应之间的关系。结果表明,PCV2 感染通过促进 3D4/2 细胞中 TNF-α、IL-1β、IL-6 和 IL-10 的分泌诱导炎症。苦参多糖处理后,细胞中 TNF-α、IL-1β 和 IL-6 的产生及其 mRNA 表达水平明显降低,而 IL-10 的水平和 mRNA 表达升高。SSP 还降低了 PCV2 感染细胞中 HATs、组蛋白 H3 乙酰化(Ac-H3)和组蛋白 H4 乙酰化(Ac-H4)、p65 磷酸化(P-p65)的活性,同时下调了 HDACs 的活性,这涉及到 SSP 对组蛋白乙酰化和 NF-κB 信号通路激活的抑制作用。HAT1mRNA 表达下调和 HDAC1mRNA 表达上调进一步支持 SSP 对组蛋白乙酰化的抑制作用。综上所述,苦参多糖通过组蛋白乙酰化和 NF-κB 信号通路拮抗 PCV2 诱导的炎症反应。