title: Urotensin II induces interleukin 8 expression in human umbilical vein endothelial cells.
abstract: BACKGROUND
  Urotensin II (U-II), an 11-amino acid peptide, exerts a wide range of actions in cardiovascular systems. Interleukin-8 (IL-8) is secreted by endothelial cells, thereby enhancing endothelial cell survival, proliferation, and angiogenesis. However, the interrelationship between U-II and IL-8 as well as the detailed intracellular mechanism of U-II in vascular endothelial cells remain unclear. The aim of this study was to investigate the effect of U-II on IL-8 expression and to explore its intracellular mechanism in human umbilical vein endothelial cells.
  
  
  RESULTS
  Primary human umbilical vein endothelial cells were used. Expression of IL-8 was determined by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and luciferase reporter assay. Western blot analyses and experiments with specific inhibitors were performed to reveal the downstream signaling pathways as concerned. U-II increased the mRNA/protein levels of IL-8 in human umbilical vein endothelial cells. The U-II effects were significantly inhibited by its receptor antagonist [Orn(5)]-URP. Western blot analyses and experiments with specific inhibitors indicated the involvement of phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase in U-II-induced IL-8 expression. Luciferase reporter assay further revealed that U-II induces the transcriptional activity of IL-8. The site-directed mutagenesis indicated that the mutation of AP-1 and NF-kB binding sites reduced U-II-increased IL-8 promoter activities. Proliferation of human umbilical vein endothelial cells induced by U-II could be inhibited significantly by IL-8 RNA interference.
  
  
  CONCLUSIONS
  The results show that U-II induces IL-8 expression in human umbilical vein endothelial cells via p38 mitogen-activated protein kinase and extracellular signal-regulated kinase signaling pathways and IL-8 is involved in the U-II-induced proliferation of human umbilical vein endothelial cells.
authors.affiliation: Department of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Cardiovascular Surgery, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Yi-Tin
authors.initials: YT
authors.lastname: Tsai
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Shih-Hurng
authors.initials: SH
authors.lastname: Loh
authors.affiliation: Department of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China.
authors.forename: Ju-Chi
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Department of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China ; Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China.
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China ; Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Hung-Hsing
authors.initials: HH
authors.lastname: Chao
authors.affiliation: Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, China Medical University, Taichung, Taiwan, Republic of China ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Jin-Jer
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014579:Urotensins / Q000502:physiology*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D014579:Urotensins; C029677:urotensin II