CHENG-CHUNG FANGTZUNG-HSIN CHOUJENQ-WEN HUANGCHIEN-CHANG LEESHYR-CHYR CHEN2019-11-122019-11-122018-06-212045-2322https://scholars.lib.ntu.edu.tw/handle/123456789/431102Peritoneal 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.en[SDGs]SDG3antiinflammatory 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 Adhesionsjournal article10.1038/s41598-018-25994-5299302812-s2.0-85072528225WOS:000435790500060https://api.elsevier.com/content/abstract/scopus_id/85072528225