| Project/Area Number |
24791136
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Chiba University |
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Principal Investigator |
SATOH Takashi 千葉大学, 大学院・医学研究院, 助教 (90568635)
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| Project Period (FY) |
2012 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 細胞死 / インフラマソーム / 自然免疫 / NLRP3 / ネクローシス / プログラム細胞死 / 好中球 |
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| Research Abstract |
Mutant-NLRP3 expression by Tet-on system induced necrotic cell death, while WT did not. We showed that CA074-Me(casepsin B inhibitor)and Z-VAD-fmk(pan-caspase inhibitor)blocked the mutant-NLRP3 dependent cell death before and after ASC oligomerization, respectively. Knocking down of ASC and caspase-1 by sh-RNA revealed that ASC was required in NLRP3-induced necrotic cell death, whereas caspase-1 was not. We judged the manner of cell death induced by NLRP3-PYD oligomerization as necrosis from several observations, but when NLRP3-PYD was oligomerized, we observed the activation of caspase-3 and PARP, which is observed in apoptosis and was not observed in mutant NLRP3 expression by tet-on system. This indicates that this NLRP3-PYD oligomerization model cannot be a good model of NLRP3 activation. We performed neutrophil infiltration assays using an air-pouch model. This assay showed that NLRP3-mediated necrotic cell death resulted in a neutrophilic inflammatory response without IL-1β.
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