2015 Fiscal Year Final Research Report
Discovery of therapeutic targets for Sjogren's syndrome
| 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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| Keywords | シェーグレン症候群 / BAFF / シグナル伝達経路 |
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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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| Free Research Field |
臨床免疫学
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