| Project/Area Number |
12670976
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YAMAMOTO Koh Tokyo Medical and Dental University, Research Assistant, 医学部・附属病院, 助手 (00281717)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Interleukin-12 / Transcription factor / STAT4 / Perforin / インターロイキンー12 |
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| Research Abstract |
Interleukin (IL)-12 induces tyrosine phosphorylation and activation of signal transducer and activator of transcription (STAT) 4, stimulates proliferation of natural killer (NK) cells, enhances NK cell-mediated cytolytic activity, and induces interferon (IFN)-γ production by NK cells. STAT4-deficient mice display lack of responsiveness to IL-12 and reduced NK cell function. The pore-forming protein perforin is a key effecter protein for NK cell and CTL-mediated cytolysis. In response to IL-12, expression of perforin gene was induced in human NK cell line, NKL. The promoter region of human perforin gene contained 17 bases spaced STAT binding sequences. Electrophoretic mobility shift assay (EMSA) analysis using a probe containing the STAT binding sequence of the perforin promoter showed that this region binds with STAT4. Mutation of either of tandem STAT binding sequences resulted in down-regulation of DNA-binding capacity and promoter activity. These results demonstrated that perforin is a direct target gene of IL-12/STAT4 signal transduction pathway in NK cells, and tandem STAT binding sites in perforin promoter region play a central role for the expression. Our results suggest that tetramer of STAT4 binds to perforin promoter.
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