激活素A诱导树突样细胞分化及巨噬细胞成熟的作用研究

发布时间：2019-03-31 08:19

【摘要】： 激活素A(Activin A)属于转化生长因子-β(TGF-β)超家族成员,我们研究发现Activin A在抑制LPS活化小鼠单核巨噬细胞系RAW264.7细胞分泌IL-1β的同时,下调CD68表达。RAW264.7细胞具有向巨噬细胞和树突状细胞(DC)分化的潜能,CD68是巨噬细胞成熟标志之一。Activin A下调RAW264.7细胞CD68的表达,是其诱导细胞向DC分化还是抑制巨噬细胞活化成熟,其机制仍不清楚。因此,为深入探讨Activin A诱导RAW264.7分化、成熟的免疫调节作用,本研究采用Activin A刺激RAW264.7细胞,通过光学显微镜观察细胞形态学变化,ELISA检测IL-12,Griess法测定NO水平,流式细胞仪分析DC和巨噬细胞表面标志CD11c、CD40、CD80、CD86、MHCⅡ、CD14和CD68的表达。结果显示,Activin A能诱导RAW 264.7细胞向DC分化成熟,进一步检测发现激活素受体相互作用蛋白2 b(ARIP2b)可能是介导Activin A诱导单核细胞向DC分化的关键性信号传导分子。另一方面,骨髓造血干细胞具有分化DC的能力,而骨髓间充质干细胞能否分化为DC,仍无明确报道,而我们发现小鼠骨髓间充质干细胞能分化为单核样细胞,因此,进一步采用Activin A刺激小鼠骨髓间充质干细胞,结果显示可明显上调细胞表面DC标志CD11c和CD86表达,促进IL-12分泌,提示Activin A能诱导骨髓间充质干细胞分化为DC。腹腔巨噬细胞是组织中分化成熟的单核细胞,Activin A对成熟的巨噬细胞是否也有进一步诱导分化作用,仍未见报道。因此,研究采用Acitivin A体内外刺激小鼠腹腔巨噬细胞,结果发现,Activin A能明显促进小鼠腹腔巨噬细胞活性及进一步成熟,但不能向DC分化。 上述研究结果表明,Activin A可能通过诱导DC分化成熟增强机体获得性免疫应答能力,通过促进组织来源的巨噬细胞进一步成熟,增强巨噬细胞的天然免疫应答能力。
[Abstract]:Activin A (Activin A) is a member of the transforming growth factor-尾 (TGF- 尾) superfamily. We found that Activin A inhibited the secretion of IL-1 尾 by LPS-activated mouse monocyte-macrophage RAW264.7 cells at the same time. RAW264.7 cells have the potential to differentiate into macrophages and dendritic cells (DC). CD68 is one of the markers of macrophage maturation. Activin A down-regulates the expression of CD68 in RAW264.7 cells, and RAW264.7 cells have the potential to differentiate into macrophages and dendritic cells (DC). Whether it can induce the differentiation of cells to DC or inhibit the activation and maturation of macrophages is still unclear. Therefore, in order to investigate the effect of Activin A on RAW264.7 differentiation and mature immune regulation, RAW264.7 cells were stimulated by Activin A in this study. The morphological changes of RAW264.7 cells were observed by optical microscope, and the level of NO was detected by ELISA assay. The expression of DC and macrophage surface markers CD11c,CD40,CD80,CD86,MHC 鈪，

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