Effects of an increase of the intracellular Zn2+ via TRPA1 on the regulation of rheumatoid arthritis synoviocyte function.
| Project/Area Number |
24790267
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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 |
General pharmacology
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| Research Institution | Aichi Gakuin University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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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: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | TRPA1 / 関節リウマチ / 細胞内亜鉛 / 亜鉛トランスポータ / TRP channel |
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| Research Abstract |
We showed that inflammatory cytokines (TNFalpha and IL-1alpha) induced TRPA1 expression via nuclear factor-kappaB signaling and downstream activation of the transcription factor HIF1alpha in human fibroblast-like synoviocytes. The induced TRPA1 channels, which were intrinsically activated by intracellular Zn2+, suppressed secretion of IL-6 and IL-8. Inflammatory cytokines induced zinc transporters (ZIP8 and ZIP14) gene expression and increased intracellular Zn2+ concentration in inflammatory synoviocytes. These data suggest that intracellular Zn2+ regulate cytokine release through TRPA1 activation and may modulate the progression of Rhmotoid Arthrithis.
Moreover, we showed that auranofin, a disease-modifying antirheumatic drug (DMARD), and five NADPH oxidase (NOX) inhibitors effectively activated human TRPA1 channels.
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Report
(3 results)
Research Products
(20 results)
