Leukotriene D4 Stimulates the Migration but Not Proliferation of Endothelial Cells Mediated by the Cysteinyl Leukotriene CysLT1 Receptor via the Extracellular Signal-Regulated Kinase Pathway

Journal of Pharmacological Sciences

Er-Qing Wei²  Wen-Zhen Shi²  Li-Hui Zhang¹  Li-Ying Liu²  San-Hua Fang²  Xiao-Dong Qian³  Li-Hua Xu²  Wei-Ping Zhang²  Yun-Bi Lu²  Yu-Mei Yuan² 

[1] Department of Pharmacology, School of Basic Medicine, Hangzhou Normal University, China;Department of Pharmacology, School of Medicine, Zhejiang University, China;Department of Pharmacy, Huzhou Central Hospital, China

关键词: cysteinyl leukotriene receptor 1 (CysLT1);    endothelial cell;    proliferation;    migration;    extracellular signal-regulated kinase (ERK) 1/2;   

DOI  :  10.1254/jphs.08321FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(43)Cited-By(17)The actions of cysteinyl leukotrienes (CysLTs) are mediated by activating CysLT receptors, CysLT1, and CysLT2. The CysLT1 receptor mediates vascular responses to CysLTs; however, its effect on the proliferation and migration of endothelial cells is not clarified. To determine this effect, we observed proliferation and migration in EA.hy926 cells, a human endothelial cell line, and the involvement of activation of mitogen-activated protein kinases (MAPKs). We found that LTD4 did not affect the proliferation, but significantly stimulated the migration of endothelial cells. LTD4 also induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, but not those of p38 or JNK. The LTD4-induced migration and ERK1/2 phosphorylation were blocked by the CysLT1-receptor antagonist montelukast and the dual antagonist Bay u9773, but not by the CysLT2-receptor antagonist Bay cysLT2; the migration was also inhibited by the ERK1/2 inhibitor U0126. Our findings indicate that LTD4 stimulates the CysLT1 receptor–mediated migration of endothelial cells; this may be regulated by the ERK1/2 pathway.

【 授权许可】

Unknown