Plasmin inhibition protects against severe acute inflammation in solid organs.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861215
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Juntendo University
• Principal Investigator: TASHIRO Yoshihiko 順天堂大学, 医学部, 助教 (20636245)
• Co-Investigator(Renkei-kenkyūsha): HATTORI Koichi 順天堂大学大学院, 医学研究科, 特任先任准教授 (10360116)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 急性肝炎 / 急性膵炎 / 炎症性サイトカイン / MMP9 / TNFα / 線維素溶解系 / プラスミン / 実質臓器

Outline of Final Research Achievements

Treatment of severe inflammation in solid organs such as acute hepatitis and pancreatitis is still high mortality. It is known inflammatory cytokines in severe inflammation of solid organs is important, and its secretion is dependent on proteases like matrix metalloproteinases (MMP). There are some suggestions that MMPs are the predominant proteinases expressed in solid organ during sever inflammation. Others and we showed that plasmin can activate several MMPs.
Here, we investigated the function of MMP9 and plasminogen(plg) in an animal model of severe acute hepatitis. Pharmacological inhibition of plasmin or targeted gene deletion of Plg or MMP9 prevented high mortality of severe acute hepatitis. This was associated with a reduced inflammatory cell infiltration in hepatocyte and correlated with impaired cytokine level elevation. In summary, our data show that pharmacological inhibition of plasmin or the absence of Plg/MMP9 strongly inhibit the inflammatory response.

Free Research Field

消化器外科