【摘要】： 激活素A(Activin A)屬于轉化生長因子-β(TGF-β)超家族成員,我們研究發(fā)現(xiàn)Activin A在抑制LPS活化小鼠單核巨噬細胞系RAW264.7細胞分泌IL-1β的同時,下調CD68表達。RAW264.7細胞具有向巨噬細胞和樹突狀細胞(DC)分化的潛能,CD68是巨噬細胞成熟標志之一。Activin A下調RAW264.7細胞CD68的表達,是其誘導細胞向DC分化還是抑制巨噬細胞活化成熟,其機制仍不清楚。因此,為深入探討Activin A誘導RAW264.7分化、成熟的免疫調節(jié)作用,本研究采用Activin A刺激RAW264.7細胞,通過光學顯微鏡觀察細胞形態(tài)學變化,ELISA檢測IL-12,Griess法測定NO水平,流式細胞儀分析DC和巨噬細胞表面標志CD11c、CD40、CD80、CD86、MHCⅡ、CD14和CD68的表達。結果顯示,Activin A能誘導RAW 264.7細胞向DC分化成熟,進一步檢測發(fā)現(xiàn)激活素受體相互作用蛋白2 b(ARIP2b)可能是介導Activin A誘導單核細胞向DC分化的關鍵性信號傳導分子。另一方面,骨髓造血干細胞具有分化DC的能力,而骨髓間充質干細胞能否分化為DC,仍無明確報道,而我們發(fā)現(xiàn)小鼠骨髓間充質干細胞能分化為單核樣細胞,因此,進一步采用Activin A刺激小鼠骨髓間充質干細胞,結果顯示可明顯上調細胞表面DC標志CD11c和CD86表達,促進IL-12分泌,提示Activin A能誘導骨髓間充質干細胞分化為DC。腹腔巨噬細胞是組織中分化成熟的單核細胞,Activin A對成熟的巨噬細胞是否也有進一步誘導分化作用,仍未見報道。因此,研究采用Acitivin A體內外刺激小鼠腹腔巨噬細胞,結果發(fā)現(xiàn),Activin A能明顯促進小鼠腹腔巨噬細胞活性及進一步成熟,但不能向DC分化。 上述研究結果表明,Activin A可能通過誘導DC分化成熟增強機體獲得性免疫應答能力,通過促進組織來源的巨噬細胞進一步成熟,增強巨噬細胞的天然免疫應答能力。
[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，

本文編號：2450734