Analysis of the acute pancreatitis in the mice deficient for the IRF-2 gene

IRF-2基因缺陷的小鼠(IRF-2；-/-&gt；小鼠)在PolyI：PolyC注射或病毒感染后发生急性胰腺炎。注射PolyI：PolyC后，IRF-2、-/-、GT；小鼠脾组织中IL-17、IL-22mRNA的表达显著增加。而在体外实验中，IRF-2^&lt；-/-&gt；和IRF-2^&lt；+/+&gt；PolyI：PolyC处理的脾细胞在IL-17和IL-22mRNA的表达水平上没有差异。在骨髓移植分析中，注射PolyI：PolyC后，骨髓IRF-2^&lt；+/-&gt；小鼠血清淀粉酶水平升高。对NF-kB或STAT3的凝胶位移分析显示，IRF-2^&lt；+/+&gt；与IRF-2^&lt；-/-&gt；胰腺核提取物的条带不同。在IRF-2抗体存在的情况下，IRF-2^&lt；+/+&gt；样品的复合体不发生超位。免疫印迹法未检测到P65和STAT3在IRF-2；-/-&GT；胰腺蛋白中的表达。提示IRF-2；-/-&gt；小鼠胰腺可能是PolyI：PolyC诱导的急性胰腺炎的发病机制。IRF-2^&lt；+/+&gt；和IRF-2^&lt；-/-&gt；胰腺之间的基因芯片分析目前正在我们实验室进行。PolyI：PolyC处理IRF-1^&lt；-/-&gt；-/-&gt；IRF-2^&lt；-/-&gt；双基因敲除小鼠的血清淀粉酶水平与IRF-2^&lt；-/-&gt；小鼠相似，但PolyI：PolyC处理的TRIF-1^&lt；-/-&gt；IRF-2^&lt；-/-&gt；小鼠的血清淀粉酶略有升高。这些结果提示RIG-I和MDA5而不是IRF-1可能与PolyI：PolyC诱导的IRF-2^&lt；-/-&gt；小鼠急性胰腺炎有关。IL-22受体在胰腺和皮肤上检测到，但不在免疫细胞上检测到。我们实验室正在进行IL-22受体-/-IRF-2-/-双基因敲除小鼠的产生，我们试图分析这些小鼠对PolyI：PolyC的治疗。

The mice deficient for the IRF-2 gene (IRF-2^<-/-> mice) developed acute pancreatitis after polyI:polyC injection or virus infection. The expression of IL-17 and IL-22 mRNA significantly increased in spleen of IRF-2^<-/-> mice with polyI:polyC injection. However in vitro assay, there was no difference between IRF-2^<-/-> and IRF-2^<+/+> polyI:polyC treated spleen cells in the expression levels of IL-17 and IL-22 mRNA. In bone marrow transplantation analysis, the serum amylase levels increased in IRF-2^<-/-> mice with IRF-2^<+/-> bone marrow after polyI:polyC injection. The gel shift analyses for NF-kB or STAT3 showed the different band-pattern between IRF-2^<+/+> and IRF-2^<-/-> pancreas nuclear extract. The complex from IRF-2^<+/+> sample was not supershifted in the presence of IRF-2 antibody. The proteins of p65 and STAT3 were not detected in IRF-2^<-/-> pancreas protein by the immunoblotting. These results suggested that pancreas from IRF-2^<-/-> mouse may be responsible for the polyI:polyC induced acute pancreatitis. The microarray analysis between IRF-2^<+/+> and IRF-2^<-/-> pancreas is currently underway in our laboratory. The serum amylase level of polyI:polyC treated IRF-1^<-/->IRF-2^<-/-> double knockout mice increased similar to that of IRF-2^<-/-> mice, but polyI:polyC treated TRIF^<-/->IRF-2^<-/-> mice showed slightly increased the serum amylase. These results suggested that RIG-I and MDA5, but not IRF-1 may be related to polyI:polyC induced acute pancreatitis in IRF-2^<-/-> mice. IL-22 receptor is detected on pancreas and skin, but not immune cells. The generation of IL-22 receptor-/-IRF-2-/- double knockout mice is in progress in our laboratory and we attempt to analyze those mice to polyI:polyC treatment.