2014 Fiscal Year Final Research Report
Regulation of inflammation associated with cell death
| Project/Area Number |
24390100
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Toho University (2014)
Juntendo University (2012-2013) |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Keywords | アポトーシス / ネクローシス / cFLIP / 肝炎 / 腸炎 / 皮膚炎 / 骨髄移植 / TNFa |
|---|
| 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.
|
| Free Research Field |
生化学
|
