信号调节蛋白α在天然免疫激活中的负性调节作用和机制研究

发布时间：2018-08-29 19:45

【摘要】： 天然免疫反应中TLR的激活可引起MAPKs和NF-kB的激活。信号调节蛋白SIRPα参与对MAPK和NF-kB信号通路的调节。SIRPα在LPS引起的天然免疫激活具有苇要的负性调节作用。LPS刺激后巨噬细胞SIRPα表达明显下调,这对于LPS诱导的初始天然免疫激活是必要的。干扰SIRPα后引起MAPKs和NF-kB信号通路的激活增强,一些前炎症因了的释放增多。尾静脉输入SIRPα干扰后的巨噬细胞的小鼠对LPS引起的内毒素休克敏感性显著增高,重要脏器的炎症反应明显增强。SIRPα引起以上的负性调节作用可能主要通过抑制SHP-2和下游IKK家族蛋白结合发挥作用。
[Abstract]:Activation of TLR in innate immune response can induce activation of MAPKs and NF-kB. Signal regulatory protein SIRP 伪 involved in regulation of MAPK and NF-kB signaling pathway. SIRP 伪 down-regulated the expression of SIRP 伪 in macrophages induced by LPS. This is necessary for the initial innate immune activation induced by LPS. After interfering with SIRP 伪, the activation of MAPKs and NF-kB signaling pathway was enhanced, and some proinflammatory factors were increased. The sensitivity of macrophages induced by SIRP 伪 to endotoxic shock induced by LPS was significantly increased in mice injected into caudal vein. The inflammatory response of important organs is significantly enhanced. SIRP 伪 may play a role in inhibiting the binding of SHP-2 and downstream IKK family proteins.
【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R392

【共引文献】