Leukotriene D4 stimulates the migration but not proliferation of endothelial cells mediated by the cysteinyl leukotriene cyslt(1) receptor via the extracellular signal-regulated kinase pathway.
The actions of cysteinyl leukotrienes (CysLTs) are mediated by activating CysLT receptors, CysLT(1), and CysLT(2). The CysLT(1) 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 LTD(4) did not affect the proliferation, but significantly stimulated the migration of endothelial cells. LTD(4) also induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, but not those of p38 or JNK. The LTD(4)-induced migration and ERK1/2 phosphorylation were blocked by the CysLT(1)-receptor antagonist montelukast and the dual antagonist Bay u9773, but not by the CysLT(2)-receptor antagonist Bay cysLT2; the migration was also inhibited by the ERK1/2 inhibitor U0126. Our findings indicate that LTD(4) stimulates the CysLT(1) receptor-mediated migration of endothelial cells; this may be regulated by the ERK1/2 pathway.
Yuan
Yu-Mei
YM
Department of Pharmacology, School of Medicine, Zhejiang University, China.
Fang
San-Hua
SH
Qian
Xiao-Dong
XD
Liu
Li-Ying
LY
Xu
Li-Hua
LH
Shi
Wen-Zhen
WZ
Zhang
Li-Hui
LH
Lu
Yun-Bi
YB
Zhang
Wei-Ping
WP
Wei
Er-Qing
EQ
D000085:Acetates / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003521:Cyclopropanes; D042783:Endothelial Cells / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000187:drug effects*; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology; D013440:Sulfides
D000085:Acetates; C071435:BAY u9773; D002070:Butadienes; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D020024:Leukotriene Antagonists; D009570:Nitriles; D011804:Quinolines; D018077:Receptors, Leukotriene; D013189:SRS-A; D013440:Sulfides; C113580:U 0126; D017998:Leukotriene D4; D048049:Extracellular Signal-Regulated MAP Kinases; C083169:leukotriene D4 receptor; C093875:montelukast