• 作者： Hung-Hsing Chao, Po-Yuan Chen, Wen-Rui Hao, Wei-Ping Chiang, Tzu-Hurng Cheng, Shih-Hurng Loh, Yuk-Man Leung, Ju-Chi Liu, Jin-Jer Chen and Li-Chin Sung
• 作者服務機構： 1. Division of Cardiovascular Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen Chang Road, Shih Lin District, Taipei City, Taiwan 2. Department of Surgery, School of Medicine, Taipei Medical University, Taipei 11031, Taiwan 3. Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, No.91, Hsueh-Shih Road, Taichung, Taiwan 4. Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng RdZhonghe District, New Taipei City 23561, Taiwan 5. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
• 中文摘要：
• 英文摘要：
  Background
  This study investigated whether lipopolysaccharide (LPS) increase protease-activated receptor-2 (PAR-2) expression and enhance the association between PAR-2 expression and chemokine production in human vascular endothelial cells (ECs).
  
  Methods
  The morphology of ECs was observed through microphotography in cultured human umbilical vein ECs (EA. hy926 cells) treated with various LPS concentrations (0, 0.25, 0.5, 1, and 2 μg/mL) for 24 h, and cell viability was assessed using the MTT assay. Intracellular calcium imaging was performed to assess agonist (trypsin)-induced PAR-2 activity. Western blotting was used to explore the LPS-mediated signal transduction pathway and the expression of PAR-2 and adhesion molecule monocyte chemoattractant protein-1 (MCP-1) in ECs.
  
  Results
  Trypsin stimulation increased intracellular calcium release in ECs. The calcium influx was augmented in cells pretreated with a high LPS concentration (1 μg/mL). After 24 h treatment of LPS, no changes in ECs viability or morphology were observed. Western blotting revealed that LPS increased PAR-2 expression and enhanced trypsin-induced extracellular signal-regulated kinase (ERK)/p38 phosphorylation and MCP-1 secretion. However, pretreatment with selective ERK (PD98059), p38 mitogen-activated protein kinase (MAPK) (SB203580) inhibitors, and the selective PAR-2 antagonist (FSLLRY-NH2) blocked the effects of LPS-activated PAR-2 on MCP-1 secretion.
  
  Conclusions
  Our findings provide the first evidence that the bacterial endotoxin LPS potentiates calcium mobilization and ERK/p38 MAPK pathway activation and leads to the secretion of the pro-inflammatory chemokine MCP-1 by inducing PAR-2 expression and its associated activity in vascular ECs. Therefore, PAR-2 exerts vascular inflammatory effects and plays an important role in bacterial infection-induced pathological responses.
• 中文關鍵字：
• 英文關鍵字： Lipopolysaccharides, Protease-activated receptor-2, Endothelial cells, Monocyte chemoattractant protein-1, Mitogen-activated protein kinases