| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Thrombomodulin (TM), an endothelial anticoagulant protein, neutralizes thrombin. Recombinant human thrombomodulin (rTM), anticoagulant agent, has been approved for the treatment of DIC in Japan.
The experiment yielded the following results: (1) LPS induced NET formation in human neutrophils co-cultured with platelets. NET formation was reduced by rTM. (2) In the LPS-induced septic shock model in mice, the lethality and production of serum cytokines, such as TNFa, IL-6, MCP-1, and IL-10 was lower in rTM-treated mice than in control mice. (3) Furthermore, histological studies of mouse liver revealed that rTM reduced the infiltration of neutrophils and NET formation, which was induced by LPS injection.
These results suggest that rTM may play a novel role in the NET formation and is effective in the LPS-induced septic shock model by suppressing NETs in liver and level of cytokines in blood, which resulted in the prevention of a decrease in lethality.
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