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題名: | Lipopolysaccharide pretreatment increases protease-activated receptor-2 expression and monocyte chemoattractant protein-1 secretion in vascular endothelial cells. |
作者: | 宋立勤 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, Li-Chin Sung |
貢獻者: | 醫學系內科學科心臟血管內科 |
日期: | 2017-11 |
上傳時間: | 2025-03-31 14:47:07 (UTC+8) |
摘要: | Abstract 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. |
關聯: | J Biomed Sci. 2017 Nov 15; 24(1): 85 |
描述: | 【110-2 升等】臺北醫學大學教師升等專門著作 職別:專任 送審等級:教授 著作送審 |
資料類型: | article |
顯示於類別: | [教師升等送審著作] 110
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