Cilostazol enhances IL-1β-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway

被引:18
作者
Ito, C [1 ]
Kusano, E [1 ]
Akimoto, T [1 ]
Takeda, S [1 ]
Sasaki, N [1 ]
Umino, T [1 ]
Iimura, O [1 ]
Ando, Y [1 ]
Asano, Y [1 ]
机构
[1] Jichi Med Sch, Dept Nephrol, Minami Kawachi, Tochigi 3290498, Japan
关键词
cilostazol; inducible nitric oxide synthase; vascular smooth muscle; interleukin-1; beta; apoptosis; protein kinase A;
D O I
10.1016/S0898-6568(02)00004-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Interleukin-1beta (IL-1beta) stimulates nitric oxide (NO) production and induces apoptosis in several tissues. Cilostazol is a Type 3 phosphodiesterase inhibitor. We investigated whether cilostazol affects IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle cells. Cilostazol (100 nM-10 muM) potentiated NO production triggered by IL-1beta. The mRNA and protein expression of inducible NO synthase was also upregulated by cilostazol. KT5720, an inhibitor of protein kinase A, and N-G-monomethyl-L-arginine, an inhibitor of NO synthase, abrogated cilostazol-enhanced IL-1beta-stimulated NO production and apoptosis. These results shows that cilostazol potentiates IL-1beta-induced NO production via PKA-pathway and thereafter augments apoptosis via NO-dependent pathway. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:625 / 632
页数:8
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