title: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sequentially upregulates nitric oxide and prostanoid production in primary human endothelial cells.
abstract: Endothelial cells express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors, but the function of TRAIL in endothelial cells is not completely understood. We explored the role of TRAIL in regulation of key intracellular signal pathways in endothelial cells. The addition of TRAIL to primary human endothelial cells increased phosphorylation of endothelial nitric oxide synthase (eNOS), NOS activity, and NO synthesis. Moreover, TRAIL induced cell migration and cytoskeleton reorganization in an NO-dependent manner. TRAIL did not activate the NF-kappaB or COX-2 pathways in endothelial cells. Instead, TRAIL increased prostanoid production (PGE2=PGI2>TXA2), which was preferentially inhibited by the COX-1 inhibitor SC-560. Because NO and prostanoids play a crucial role in the state of blood vessel vasodilatation and angiogenesis, our data suggest that TRAIL might play an important role in endothelial cell function.
authors.affiliation: Department of Normal Human Morphology, University of Trieste, Via Manzoni 16, 34138 Trieste. zauli@units.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
authors.forename: Assunta
authors.initials: A
authors.lastname: Pandolfi
authors.forename: Arianna
authors.initials: A
authors.lastname: Gonelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Di Pietro
authors.forename: Simone
authors.initials: S
authors.lastname: Guarnieri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: Rosalba
authors.initials: R
authors.lastname: Rana
authors.forename: Marco
authors.initials: M
authors.lastname: Vitale
authors.forename: Paola
authors.initials: P
authors.lastname: Secchiero
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009578:Nitrobenzenes / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D012694:Serine / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000199:Actins; D051017:Apoptosis Regulatory Proteins; D002867:Chromones; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D009025:Morpholines; D009578:Nitrobenzenes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009569:Nitric Oxide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D012694:Serine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester