Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 109, Issue 2, Pages 285-292Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.08321FP
Keywords
cysteinyl leukotriene receptor 1 (CysLT(1)); endothelial cell; proliferation; migration; extracellular signal-regulated kinase (ERK) 1/2
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Funding
- National Natural Science Foundation of China [30772561, 30500613, 30801397]
- Scientific Foundation of Education Ministry of China [20050335105]
- Zhejiang Provincial Natural Science Foundation of China [Y207343]
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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 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 EPK1/2 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 cysLT(2); the migration was also inhibited by the ERK1/2 inhibitor U0126. Our findings indicate that LTD4 stimulates the CysLT(1) receptor-mediated migration of endothelial cells; this may be regulated by the ERK1/2 pathway.
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