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.
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.
Zhou
Guangyi
G
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing Jiangsu Province, 210002, PR China.
Zhou
Zhiming
Z
Ge
Song
S
Liu
Dezhi
D
Zhang
Renliang
R
Xu
Gelin
G
Zhu
Wusheng
W
Yin
Qin
Q
Chen
Alex F
AF
Liu
Xinfeng
X
D000085:Acetates / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003521:Cyclopropanes; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000502:physiology*; D020024:Leukotriene Antagonists / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D018077:Receptors, Leukotriene / Q000096:biosynthesis*; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology; D013440:Sulfides; D013997:Time Factors; D014471:Umbilical Veins / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects*
D000085:Acetates; C071435:BAY u9773; D003521:Cyclopropanes; D020382:Interleukin-18; D020024:Leukotriene Antagonists; D011804:Quinolines; D018077:Receptors, Leukotriene; D013189:SRS-A; D013440:Sulfides; C412375:cysteinyl leukotriene receptor 2; C093875:montelukast