title: LPS and TNF-α induce expression of sphingosine-1-phosphate receptor-2 in human microvascular endothelial cells.
abstract: Sphingosine-1-phosphate (S1P) is a bioactive sophospholipid with various S1P receptor (S1PR) expression profiles in cells of different origin. S1PR1, R3 and - to a lesser extent - R2 were the main receptors expressed in most of endothelial cells (ECs). The balances in the expression and activation of S1PR1, R2 and R3 help to maintain the physiological functions of ECs. Reverse transcription-PCR and Western blotting were used to detect the mRNA transcript level and protein expression of S1PR. Endothelial barrier function was measured by transflux of tracer protein through endothelial monolayer. Human dermal microvascular ECs predominantly expressed S1PR1 and S1PR3. Lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) significantly upregulated S1PR2 mRNA and protein levels. The application of S1PR2 antagonist JTE-013 decreased the endothelial monolayer hyper-permeability response induced by LPS and TNF-α. Inflammatory mediators LPS and TNF-α induce S1PR2 expression in endothelium, suggesting that S1PR2 up-regulation may be involved in LPS and TNF-α elicited endothelial barrier dysfunction.
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong Province, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.forename: Chong
authors.initials: C
authors.lastname: Zeng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.forename: Xuliang
authors.initials: X
authors.lastname: Huang
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
mesh_terms: D015153:Blotting, Western; D002199:Capillary Permeability; D002478:Cells, Cultured; D020405:Dermis / Q000098:blood supply*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D018836:Inflammation Mediators / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000081025:Sphingosine-1-Phosphate Receptors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D018836:Inflammation Mediators; C471998:JTE 013; D008070:Lipopolysaccharides; D011720:Pyrazoles; D011725:Pyridines; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; C477522:S1PR2 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D014409:Tumor Necrosis Factor-alpha