| Project/Area Number |
24659183
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Nippon Medical School |
|---|
Principal Investigator |
TANAKA Nobuyuki 日本医科大学, 医学(系)研究科(研究院), 教授 (80222115)
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| 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 / 2-Deoxy-D-glucose / 炎症 / 発癌抑制 / 炎症性腸疾患 / 関節リウマチ / 抗炎症治療 / 関節炎 / 脳梗塞 / マクロファージ |
|---|
| 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.
|
