Koll S, Goppelt-Struebe M, Hauser I, Goerig M
Department of Internal Medicine IV, Medical School, University of Erlangen-Nuernberg, Germany.
J Leukoc Biol. 1997 Jun;61(6):679-88. doi: 10.1002/jlb.61.6.679.
Coculture of a monocytic cell line (HL-60) and iliacal endothelial cells as an in vitro model of vascular inflammation was investigated for cooperative regulatory mechanisms of prostanoid synthesis under conditions of selective prestimulation. In coculture of endothelial cells and 12-O-tetradecanoylphorbol 13-acetate (TPA)-prestimulated monocytic HL-60 cells the capacity of prostanoid synthesis from arachidonic acid was strongly increased compared with monocultures. Concomitant with up-regulation of specific adhesion molecules, cyclooxygenase (COX) 2 mRNA was induced in endothelial cells in coculture independent of cell contact. HL-60 cells exhibited no alterations in mRNA expression of cyclooxygenases or thromboxane synthase. Coculture of TPA-prestimulated endothelial cells with unstimulated HL-60 cells led to a selectively increased capacity of thromboxane production. Under this condition HL-60 cells up-regulated COX1 and COX2 mRNA, whereas endothelial mRNA levels did not change. Our data demonstrate that the increase in prostanoid synthesis in coculture essentially depends on rapid induction of COX2 mRNA within 2 h.
研究了单核细胞系(HL-60)与髂骨内皮细胞的共培养作为血管炎症的体外模型,以探讨在选择性预刺激条件下前列腺素合成的协同调节机制。在内皮细胞与12-O-十四酰佛波醇-13-乙酸酯(TPA)预刺激的单核HL-60细胞的共培养中,与单培养相比,花生四烯酸合成前列腺素的能力显著增强。伴随着特异性粘附分子的上调,共培养的内皮细胞中独立于细胞接触诱导了环氧化酶(COX)2 mRNA。HL-60细胞中环氧化酶或血栓素合酶的mRNA表达无变化。TPA预刺激的内皮细胞与未刺激的HL-60细胞共培养导致血栓素产生能力选择性增加。在此条件下,HL-60细胞上调了COX1和COX2 mRNA,而内皮细胞的mRNA水平未改变。我们的数据表明,共培养中前列腺素合成的增加主要取决于2小时内COX2 mRNA的快速诱导。