Rapid Communication Dominant Expression of the CysLT2 Receptor Accounts for Calcium Signaling by Cysteinyl Leukotrienes in Human Umbilical Vein Endothelial Cells
نویسندگان
چکیده
Objective—The objective of the present study was to identify and characterize the cell-surface receptors on human umbilical vein endothelial cells (HUVECs) that transduce calcium transients elicited by cysteinyl leukotrienes (CysLTs), potent spasmogenic and proinflammatory agents with profound effects on the cardiovascular system. Methods and Results—Using quantitative reverse transcription–polymerase chain reaction, we found that HUVECs abundantly express CysLT2R mRNA in vast excess ( 4000-fold) of CysLT1R mRNA. Lipopolysaccharide, tumor necrosis factor, or interleukin-1 caused a rapid (within 30 minutes) and partially reversible suppression of CysLT2R mRNA levels. Challenge of HUVECs with BAY u9773, a specific CysLT2R agonist, triggered diagnostic Ca 2
منابع مشابه
Dominant expression of the CysLT2 receptor accounts for calcium signaling by cysteinyl leukotrienes in human umbilical vein endothelial cells.
OBJECTIVE The objective of the present study was to identify and characterize the cell-surface receptors on human umbilical vein endothelial cells (HUVECs) that transduce calcium transients elicited by cysteinyl leukotrienes (CysLTs), potent spasmogenic and proinflammatory agents with profound effects on the cardiovascular system. METHODS AND RESULTS Using quantitative reverse transcription-p...
متن کاملCysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT2 and CysLT1 receptors
Cysteinyl leukotrienes (cys-LTs), LTC₄, LTD₄, LTE₄ are potent inflammatory lipid mediators that act through two distinct G-protein-coupled receptors, CysLT₁R and CysLT₂R. Although cys-LTs are shown to induce vascular leakage and atherosclerosis, the molecular mechanism by which cys-LTs modulate endothelial function is not known. Here, we show that cys-LTs (LTC₄ and LTD₄) induce robust calcium i...
متن کاملCysteinyl leukotrienes induce P-selectin expression in human endothelial cells via a non-CysLT1 receptor-mediated mechanism.
Cysteinyl leukotrienes are bioactive lipid mediators known to possess potent proinflammatory actions. Included in these are effects on vascular endothelium to promote surface expression of the adhesion molecule P-selectin. In the present study we were interested in investigating the receptor mechanism(s) involved in cysteinyl leukotriene-induced endothelial P-selectin expression. As such we exa...
متن کاملRapid Communication Differential Leukotriene Receptor Expression and Calcium Responses in Endothelial Cells and Macrophages Indicate 5-Lipoxygenase–Dependent Circuits of Inflammation and Atherogenesis
Objective—Inflammatory infiltrates and atherosclerotic lesions emerge when monocytes adhere to endothelial cells (ECs), migrate into the subendothelial space, and become macrophages (M s). Leukotrienes (LTs), products of 5-lipoxygenase, are powerful inflammatory mediators. 5-lipoxygenase M s have been shown to increase during atherogenesis, and LT receptor (LT-R) transcripts were identified in ...
متن کاملVGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells
Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosph...
متن کامل