| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2008: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
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| Research Abstract |
This study was performed in order to analyze the function of transcription factors and the gene therapy in the pathogenesis of sepsis. Transcription factor NF-kB, AP-1 and CRE increased the activity in various major organs of septic mouse with cecal ligation and puncuture. Gene therapy using decoy oligonucleotides of the transcription factors inhibited the activity in septic mice. NF-kB induced inflammatory molecules such as chemokines and adhesion molecules in septic major organs. On the other side, AP-1 was found to be involved in increased transcription of extrinsic apoptotic signaling molecules including death receptors. Decreased AP-1 activity significantly improved survival of septic mice. However, CRE decoy oligonucleotides did not strongly linked to the transcription of inflammatory molecules and apoptosis-related molecules.
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