| Project/Area Number |
25670034
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 短鎖脂肪酸 / アレルギー / サイトカイン / ヒストンアセチル化 / 受容体 / TSLP / ケラチノサイト / ヒストン脱アセチル化酵素 / GPCR |
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| Outline of Final Research Achievements |
Thymic stromal lymphopoietin (TSLP) is known as a master cytokine which is produced by, mainly, epithelial cells and induces allergic responses. In this study, we found that short- and medium-chain fatty acids, especially valeric acid (VA) and isovaleric acid, induced TSLP production in mouse keratinocyte cell line PAM212 cells. Pharmacological analysis suggested that VA-induced TSLP production was not mediated by FFAR2/3 and olfactory receptors. ERK, Rho kinase and NF-κB pathways were involved in the VA-induced TSLP production. We found that VA increased the acetylation of histone H4. Allthough histone-deacetylase (HDAC) inhibitor tricostatin A and sodium butylate also induced TSLP production, there was no relationship between TSLP-producing activity and HDAC-inhibitory activity. These results suggested that short- and medium-chain fatty acids including VA induced TSLP production through a novel recognition mechanism.
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