| Project/Area Number |
16H07151
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Research Collaborator |
TAKAHASHI Masafumi 自治医科大学, 医学部, 教授 (40296108)
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 炎症 / 酵素 / 細胞・組織 / 肺疾患 / 免疫学 |
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| Outline of Final Research Achievements |
We investigated the role of NLRP3 inflammasome-driven IL-1β production in a mouse model of acid aspiration-induced inflammation and ALI. Acid aspiration induced inflammatory responses and ALI in wild-type mice, and these were significantly attenuated in IL-1β-knockout (KO) mice; however, acid aspiration-induced ALI and IL-1β production were not inhibited in NLRP3-KO mice. In vitro experiments revealed that acidic stress (pH 1.75) induced pro-IL-1β processing into its 20-kDa mature form (p20-IL-1β), which was different from caspase-1-processed 17-kDa form (p17-IL-1β), in human THP-1 macrophages. Acidic stress-produced p20-IL-1β was prevented by inhibitors for seine proteases (AEBSF), but not for cysteine proteases (E-64) and cathepsin G. We generated THP-1 macrophages constitutively expressing human IL-1β which have known cleavage site mutations, and found that acidic stress failed to process these mutants.
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