2013 Fiscal Year Final Research Report
Effects of an increase of the intracellular Zn2+ via TRPA1 on the regulation of rheumatoid arthritis synoviocyte function.
| Project/Area Number |
24790267
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
General pharmacology
|
|---|
| Research Institution | Aichi Gakuin University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Keywords | TRPA1 / 関節リウマチ / 細胞内亜鉛 |
|---|
| 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.
|
