RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by ind...RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I^-/- mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I^-/- mice are viable and fertile. Histological analysis shows that Rig-I^-/ mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer＇s patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation ofT-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit （Gαi2） in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.展开更多
文摘RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I^-/- mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I^-/- mice are viable and fertile. Histological analysis shows that Rig-I^-/ mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer＇s patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation ofT-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit （Gαi2） in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.
文摘目的探讨外源性Gαi2C末端肽段(Gαi2C-terminal peptide,Gαi2ctp)对迷走神经介导心房颤动(简称房颤)诱发的影响。方法健康成年家犬14只随机分为两组:对照组(n=7),给予单纯的超声微泡造影剂;实验组(n=7),给予制备好的携Gαi2ctp靶向超声造影剂。分别在高位右房(HRA)、左心耳(LAA)及左下肺静脉(LSPV)行Burst刺激,观察基础状态、迷走神经刺激、靶向转导Gαi2ctp后上述部位房颤诱发率及持续时间的变化。结果 1迷走神经刺激可显著增加心房及肺静脉各部位房颤的诱发率和持续时间。2实验组左房靶向转导Gαi2ctp后0.5、1、2 h LAA和LSPV房颤诱发率(分别为15.9%、14.3%、14.3%和17.5%、19.0%、17.5%)较基础状态(分别为31.7%和33.3%)明显下降(P<0.05);与对照组相比,实验组左心房靶向转导Gαi2ctp后LAA、LSPV房颤诱发率下降(P分别﹤0.01、0.05)。3实验组左房靶向转导Gαi2ctp后0.5、1、2 h LAA、LSPV房颤持续时间(分别为16.43±3.59、16.57±2.64、15.14±4.14 s和17.57±4.47、16.85±2.91、17.29±3.40 s)较基础状态(分别为22.01±4.83和23.29±4.27 s)下降(P<0.01)。与对照组相比,实验左房靶向转导Gαi2ctp后LAA、LSPV房颤持续时间下降,差异有显著性(P<0.01或0.05)。结论靶向转导外源性Gαi2ctp可以减少迷走神经介导房颤的发生。
