激活素调控小鼠巨噬细胞活性的信号传导机制研究

发布时间：2018-02-01 01:04

  本文关键词： 激活素 受体相互作用蛋白 信号传导 巨噬细胞 IL-1β NO RT-PCR Western blotting　出处：《吉林大学》2006年博士论文　论文类型：学位论文

【摘要】：激活素(Activin)属于TGFβ超家族成员,在神经细胞分化诱导、造血细胞增殖和分化、内分泌中枢垂体性激素分泌调节等多方面发挥重要作用,同时激活素还是组织修复、再生和分化的重要调节因子,参与机体炎症和急性期反应。巨噬细胞是参与机体炎性应答的主要细胞,前期研究发现激活素可以调控巨噬细胞分泌NO,其作用与巨噬细胞活化状态有关。本研究进一步探讨激活素对巨噬细胞活性的调节作用及其可能的信号传导机制。 巨噬细胞不仅具有分泌细胞因子、NO等作用,还是重要的吞噬细胞。因此,本研究采用原代培养C57BL/6小鼠腹腔巨噬细胞、传代培养BALB/c小鼠巨噬细胞系RAW264.7细胞为实验对象,通过分析IL-1β、NO的分泌、IL-1β、iNOS mRNA表达及细胞吞噬活性,系统探讨激活素A对巨噬细胞活性的双向调控作用。实验表明,激活素A刺激小鼠巨噬细胞炎性因子产生、增强吞噬活性,具有剂量依赖关系;而对LPS活化小鼠巨噬细胞的活性具有明显抑制作用。提示激活素对巨噬细胞的分泌活性和吞噬活性,均具有双向调节作用,此作用与巨噬细胞的激活状态有关。其作用有助于维持机体生理平衡,防止因炎症反应过度而造成的损害。 激活素对细胞的作用具有明显的组织学特异性,其作用的特异性与其受体后信号传导差异有关,前期研究表明巨噬细胞高表达激活素Ⅱ型受体(ActRⅡA)。围绕ActRⅡA信号传导途径的研究,发现了新的信号调控蛋白——激活素受体相互作用蛋白(ActRIP),为明确ActRIPs参与巨噬细胞活性调控的信号传导机制。实验采用基因过表达技术,将ActRIP2、3导入小鼠巨噬细胞,结果显示,ActRIP2抑制小鼠巨噬细胞NO的分泌及iNOS、IL-1 mRNA表达,而ActRIP3促进NO的分泌及iNOS、IL-1 mRNA表达。激活素刺激小鼠巨噬细胞
[Abstract]:Activinin, a member of TGF 尾 superfamily, plays an important role in the induction of neuronal differentiation, proliferation and differentiation of hematopoietic cells, and regulation of pituitary hormone secretion in endocrine center. At the same time activin is also an important regulator of tissue repair regeneration and differentiation involved in inflammation and acute phase reaction. Macrophages are the main cells involved in the body inflammatory response. Previous studies have shown that activin can regulate the secretion of no by macrophages. The effect of activin on the activity of macrophages and its possible signal transduction mechanism were investigated. Macrophages not only secrete cytokines, such as no, but also important phagocytes. Therefore, the primary culture of C57BL / 6 mouse peritoneal macrophages was carried out in this study. BALB/c murine macrophage cell line RAW264.7 was subcultured and the secretion of IL-1 尾 no was analyzed. The expression of iNOS mRNA and the phagocytic activity of macrophages were studied systematically. The results showed that activin A stimulated the production of macrophage inflammatory factors in mice. The phagocytic activity was enhanced in a dose-dependent manner. The activity of macrophages activated by LPS was inhibited obviously, which indicated that activin had bidirectional regulation on the secretion activity and phagocytic activity of macrophages. This action is related to the activation of macrophages. It helps to maintain the physiological balance of the body and prevent the damage caused by excessive inflammatory reaction. The effect of activin on cells is histologically specific, and its specificity is related to the difference of signal transduction after receptor. Previous studies have shown that macrophages overexpression activin type 鈪，

本文编号：1480489