https://scholars.lib.ntu.edu.tw/handle/123456789/431102
標題: | The Small Molecule Inhibitor QLT-0267 Decreases the Production of Fibrin-Induced Inflammatory Cytokines and Prevents Post-Surgical Peritoneal Adhesions | 作者: | CHENG-CHUNG FANG TZUNG-HSIN CHOU JENQ-WEN HUANG CHIEN-CHANG LEE SHYR-CHYR CHEN |
公開日期: | 21-六月-2018 | 出版社: | NATURE PUBLISHING GROUP | 卷: | 8 | 期: | 1 | 來源出版物: | Scientific reports | 摘要: | Peritoneal adhesions develop after abdominal surgery, trauma or intraperitoneal infections, and have important consequences. The deposition of peritoneal fibrin is a common pathophysiological pathway for the formation of adhesions. Here, we aimed to examine the effects of fibrin-induced cytokine production on peritoneal mesothelial cells (PMCs), and to block the effects of fibrin using an integrin-linked kinase (ILK) inhibitor, QLT-0267. PMCs were cultured from the enzymatic disaggregation of rat omentum. After the PMCs were covered with fibrin, the expression of IL-1β, IL-6, TNFα and VEGF-A increased. This increase in cytokine production was attenuated by QLT-0267, which acted via the inhibition of both the ILK and focal adhesion kinase (FAK) pathways, and subsequently via the GSK-3β pathway. We found that QLT-0267 decreased both the severity of peritoneal adhesion and the serum levels of IL-6 in our post-surgical adhesion mouse model. In conclusion, our study provides novel evidence that fibrin-induced cytokine production may involve in the mechanism of peritoneal adhesion formation. Furthermore, the use of the small molecule inhibitor QLT-0267 is a new strategy in preventing peritoneal adhesion in patients undergoing abdominal surgery. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/431102 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-018-25994-5 | SDG/關鍵字: | antiinflammatory agent; azo compound; cytokine; fibrin; integrin-linked kinase; protein kinase inhibitor; protein serine threonine kinase; pyrazole derivative; QLT 0267; animal; cell culture; drug effect; epithelium cell; genetics; Institute for Cancer Research mouse; male; metabolism; mouse; pathology; peritoneum; rat; tissue adhesion; Animals; Anti-Inflammatory Agents; Azo Compounds; Cells, Cultured; Cytokines; Epithelial Cells; Fibrin; Male; Mice; Mice, Inbred ICR; Peritoneum; Protein Kinase Inhibitors; Protein-Serine-Threonine Kinases; Pyrazoles; Rats; Tissue Adhesions |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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