| Project/Area Number |
25461483
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | シェーグレン症候群 / BAFF / シグナル伝達経路 / 単球 / B細胞 / BAFF受容体 / IL-6 / 医薬品リポジショニング / IgG |
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| Outline of Final Research Achievements |
Our in vitro experiments have shown that elevated expression level of BAFF (B cell activating factor) receptor, BR3, is associated with the pathogenesis of Sjogren’s syndrome (SS). These results suggest that inhibitors against BAFF signaling pathways through BR3 may be drug candidates for SS. In this study, we tried to identify the molecules involved in the pathways in SS monocytes, and performed drug repositioning to search for BAFF signaling inhibitors. As a result, we found that IKKa and IKKb, which are involved in NF-kB pathway, were highly phosphorylated in SS monocytes, and that NF-kB inhibitors strongly suppressed IL-6 production by BAFF-stimulated monocytes. In addition, we discovered several approved drugs inhibited IL-6 production by BAFF-stimulated monocytes. Based on these results, we will further investigate molecular mechanisms of action of these drugs as BAFF signaling inhibitors to develop novel therapies for SS.
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