title: 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.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Zhejiang University, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Yuan
authors.forename: San-Hua
authors.initials: SH
authors.lastname: Fang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Qian
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Liu
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Xu
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Shi
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Zhang
authors.forename: Yun-Bi
authors.initials: YB
authors.lastname: Lu
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhang
authors.forename: Er-Qing
authors.initials: EQ
authors.lastname: Wei
mesh_terms: 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
chemical_list: 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