| Project/Area Number |
18390124
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nagasaki University |
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Principal Investigator |
MATSUYAMA Toshifumi Nagasaki University, Graduate School of Biomedical Sciences, Professor (30165922)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,490,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2006: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | IRF-2 / acute pancreatitis / interferon / double strand RNA / interferon regulatory factors |
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| Research Abstract |
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.
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