Nanayama T, Hara S, Inoue H, Yokoyama C, Tanabe T
Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan.
Prostaglandins. 1995 Jun;49(6):371-82. doi: 10.1016/0090-6980(95)00068-l.
The mechanism responsible for the rapid increase of thromboxane A2 synthesis by cells of the human monoblastoid cell line U937, which were differentiated with 12-O-tetradecanoyl-phorbol-13-acetate, induced by lipopolysaccharide (LPS) was studied. Both RNA blot and immunoblot analyses showed that LPS increased the levels of prostaglandin endoperoxide synthase-1 (PES-1) and -2 (PES-2) in a time-dependent manner, and the modes of induction of the two isozymes differed. The maximum PES-1 mRNA level was 1.6 times higher 36 h after than before stimulation by LPS, and that of PES-2 mRNA was elevated about 20-fold at its peak at 12 h after stimulation. Consequently, the immunoreactive PES-1 and PES-2 protein levels also increased time-dependently after LPS stimulation. However, the effects of LPS on the thromboxane synthase mRNA and protein levels were much less marked. These results indicate that LPS-induced thromboxane synthesis by the differentiated cells was regulated at the levels of the two PES isozymes, predominantly at the PES-2 level.
研究了脂多糖(LPS)诱导的、经12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯分化的人单核细胞系U937细胞中血栓素A2合成快速增加的机制。RNA印迹和免疫印迹分析均表明,LPS以时间依赖性方式增加前列腺素内过氧化物合酶 - 1(PES - 1)和 - 2(PES - 2)的水平,且两种同工酶的诱导模式不同。LPS刺激后36小时,PES - 1 mRNA的最大水平比刺激前高1.6倍,PES - 2 mRNA在刺激后12小时达到峰值时升高约20倍。因此,LPS刺激后,免疫反应性PES - 1和PES - 2蛋白水平也随时间依赖性增加。然而,LPS对血栓素合酶mRNA和蛋白水平的影响则小得多。这些结果表明,LPS诱导的分化细胞中血栓素合成在两种PES同工酶水平上受到调节,主要在PES - 2水平。