IL-18 accelerates the cell apoptosis by up-regulating cysteinyl leukotriene 2 receptor expression in human umbilical vein endothelial cells at the early stage of administration

Vascul Pharmacol. May-Jun 2009;50(5-6):171-7. doi: 10.1016/j.vph.2009.01.006.

Abstract

The purpose of the present study is to identify whether interleukin (IL)-18 can modulate cysteinyl leukotriene 2 receptor (CysLT2R) expression in Human Umbilical Vein Endothelial Cells (HUVECs) and how it influences the cell death. According to the results from real-time reverse transcription PCR, confocal laser scanning microscopy, and western blotting, a dose-dependent augmentation of CysLT2R protein expression in HUVECs was triggered by IL-18 for the first 2 h followed by down-regulation within the next 22 h after IL-18 administration. The flow cytometry showed that non-selective CysLT1R and CysLT2R antagonist BAY-u9773 could attenuate the early stage apoptosis mediated by IL-18 whereas CysLT1R antagonist Montelukast couldn't. Also, pretreatment with BAY-u9773 suppressed calcium influx of HUVECs induced by IL-18 whereas Montelukast didn't work. The observation that progression of cell death aggravated by IL-18 could be attenuated by BAY-u9773 may offer a chance to develop a novel way to treat arteriosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology*
  • Female
  • Humans
  • Interleukin-18 / physiology*
  • Leukotriene Antagonists / pharmacology
  • Quinolines / pharmacology
  • Receptors, Leukotriene / biosynthesis*
  • SRS-A / analogs & derivatives
  • SRS-A / pharmacology
  • Time Factors
  • Umbilical Veins / physiopathology*
  • Up-Regulation / drug effects*

Substances

  • Acetates
  • BAY u9773
  • Interleukin-18
  • Leukotriene Antagonists
  • Quinolines
  • Receptors, Leukotriene
  • SRS-A
  • cysteinyl leukotriene receptor 2
  • montelukast