摘要
BACKGROUND Acute pancreatitis(AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome(SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1(PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP.AIM To investigate the role and mechanism of PSGL-1 in the development of AP.METHODS The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout(PSGL-1-/-) and wild-type(PSGL-1+/+) mice. Leukocyteendothelial cell adhesion was measured in a peripheral blood mononuclear cell(PBMC)-endothelial cell coculture system.RESULTS The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/-AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1 beta(IL-1 beta) and Interleukin-6(IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1 beta.CONCLUSION PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.
基金
Supported by National Natural Science Foundation of China,No. 81670387,No. 31671440,and No. 81800402。
作者简介
Xu Zhang,ORCID number:0000-0001-6553-1214;Ming Zhu,ORCID number:0000-0001-5631-3362;Xiao-Liang Jiang,ORCID number:0000-0001-6010-343X;Xing Liu,ORCID number:0000-0003-4738-1616;Xue Liu,ORCID number:0000-0003-1171-9064;Pan Liu,ORCID number:0000-0002-6600-5432;Xian-Xian Wu,ORCID number:0000-0001-6368-4671;Zhi-Wei Yang,ORCID number:0000-0003-3006-2512;Corresponding author:Tao Qin,MD,PhD,Doctor,Professor,Department of Hepato-Biliary-Pancreatic Surgery,Zhengzhou University People’s Hospital&Henan Provincial People’s Hospital,No.7 Weiwu Road,Zhengzhou 450003,Henan Province,E-mail:goodfreecn@163.com,ORCID number:0000-0001-8791-3555.
