2013 Fiscal Year Final Research Report
Development of novel anti-inflammation therapy against deglycosylation of proinflammatory cytokine receptors.
| Project/Area Number |
24659183
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
TANAKA Nobuyuki 日本医科大学, 医学(系)研究科(研究院), 教授 (80222115)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 炎症性疾患 / 炎症性サイトカイン / 炎症性サイトカイン受容体 / 糖鎖修飾 / シグナル伝達 / 抗炎症療法 |
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| Research Abstract |
Anti-proinflammatory cytokine therapies directed against interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha are major advancements in treating inflammatory diseases. We found that the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) attenuated cellular responses to IL-6 by inhibiting N-linked glycosylation of the IL-6 receptor gp130. Aglyco forms of gp130 failed to bind IL-6 and to activate downstream signals. Surprisingly, 2-DG completely inhibited dextran sodium sulfate-induced colitis, a mouse model for inflammatory bowel disease. We found that 2-DG also inhibited signals for TNF-alpha and IL-1beta, and accordingly prevented death by another inflammatory disease, LPS shock. Finally, orally administered 2-DG alleviated laminarin-induced arthritis in the SKG mouse an experimental model for human rheumatoid arthritis. Our results suggest that glycosylation of proinflammatory cytokine receptors is a potential target to alleviate inflammatory responses.
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[Journal Article] p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion2014
Author(s)
Yamauchi S, Hou YY, Guo AK, Hirata H, Nakajima W, Yip AK, Yu CH, Harada I, Chiam KH, Sawada Y, Tanaka N, Kawauchi K.
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Journal Title
J Cell Biol
Volume: 31
Pages: 1191-207
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