title: Leukotriene D4 enhances tumor necrosis factor-α-induced vascular endothelial growth factor production in human monocytes/macrophages.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic mitogens specific for vascular endothelial cells. It also induces vascular hyperpermeability and protein leakage into the extracellular space. Leukotriene D(4) (LTD(4)), one of the cysteinyl leukotrienes (CysLTs), is known to be one of the key molecules of allergic inflammation. The interaction between LTD(4) and VEGF production in human monocytes/macrophages is not well characterized.
  
  
  METHODS
  We examined VEGF production by THP-1 cells, a human monocytic leukemia cell line, and human peripheral blood CD14+monocytes/macrophages stimulated with LTD(4) and/or tumor necrosis factor-α (TNF-α). We also determined the inhibitory effects of pranlukast, a CysLT(1) receptor antagonist, on VEGF production by LTD(4) stimulation.
  
  
  RESULTS
  LTD(4) significantly induced VEGF production and enhanced TNF-α-induced VEGF release in THP-1 cells and human peripheral blood CD14+monocytes/macrophages. VEGF mRNA expression was also induced by stimulation of THP-1 cells with LTD(4) and TNF-α. In addition, 10(-7)-10(-10)M pranlukast completely inhibited VEGF production enhanced by LTD(4). The 50% inhibitory concentration (IC50) for VEGF production in THP-1 cells was 10(-10)-10(-11)M.
  
  
  CONCLUSIONS
  LTD(4) induced VEGF production and enhanced VEGF release induced by TNF-α via CysLT(1) receptors in human monocytes/macrophages. These effects were completely inhibited by pranlukast.
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan. k010um@yamaguchi-u.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Haneda
authors.forename: Shunji
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Reiji
authors.initials: R
authors.lastname: Hirano
authors.forename: Kunio
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Ayami
authors.initials: A
authors.lastname: Ohsaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichiyama
mesh_terms: D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017998:Leukotriene D4 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D002867:Chromones; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017998:Leukotriene D4; C047681:pranlukast