The Small Molecule Inhibitor QLT-0267 Decreases the Production of Fibrin-Induced Inflammatory Cytokines and Prevents Post-Surgical Peritoneal Adhesions

被引：30

作者：

Fang, Cheng-Chung ^{[1
,2
,3
]}

Chou, Tzung-Hsin ^{[1
,2
,4
]}

Huang, Jenq-Wen ^{[2
,3
]}

Lee, Chien-Chang ^{[1
,2
]}

Chen, Shyr-Chyr ^{[1
,2
,4
]}

机构：

[1] Natl Taiwan Univ Hosp, Dept Emergency Med, Taipei, Taiwan

[2] Natl Taiwan Univ, Coll Med, Taipei, Taiwan

[3] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan

[4] Natl Taiwan Univ Hosp, Dept Surg, Taipei, Taiwan

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

INTEGRIN-LINKED KINASE; INTRAABDOMINAL ADHESION; POSTOPERATIVE ADHESIONS; SURGERY; PATHOPHYSIOLOGY; FIBROBLASTS; ACTIVATION; DEPENDENCE; REDUCTION; HYDROGEL;

D O I：

10.1038/s41598-018-25994-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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-1 beta, IL-6, TNF alpha. 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-3 beta 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.

引用

页数：12