| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Outline of Final Research Achievements |
To investigate a role for cFLIP in tissue homeostasis, we generated conditional cFLIP-deficient mice. Hepatocyte-, intestinal epithelial cell-, and epidermis-specific cFLIP-deficient mice died perinatally due to enhanced apoptosis or necroptosis of respective tissues, suggesting that cFLIP plays an essential role in maintaining tissue homeostasis. We also generated mice, in which expressions of cFLIP in hepatocytes were decreased (cFLIPHeplow mice) to half compared to those of wild-type mice. Upon TNFα injection, cFLIPHeplow mice spontaneously developed transient and mild hepatitis. We next investigated whether Kupffer cells or infiltrated monocytes were required for suppression of inflammation associated with cell death. Depletion of infiltrated monocytes, but not Kupffer cells resulted in exacerbation of hepatitis along with strong elevation of inflammatory cytokines, suggesting that infiltrated monocytes, but not Kupffer cells play a crucial role in suppression of inflammation.
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