Maruyama I, Soejima Y, Osame M, Ito T, Ogawa K, Yamamoto S, Dittman W A, Saito H
Third Department of Internal Medicine, Kagoshima University School of Medicine, Japan.
Thromb Res. 1991 Feb 1;61(3):301-10. doi: 10.1016/0049-3848(91)90107-8.
We previously reported that the expression of thrombomodulin on the MEG-01, a cell line from human megakaryoblastic leukemia, was increased by agents that increase intracellular cAMP. In this paper we examine the effect of these agents on cultured human umbilical vein endothelial cells (HUVEC) and mouse hemangioma cells. Incubation of the cells with 3 mM dibutyryl cAMP (dbcAMP) increased functionally active thrombomodulin by about 2-fold on HUVEC and 4-fold on hemangioma cells. This effect was observed from 1 hour after the incubation and continued up to 24 hours. Dot hybridization of mRNA demonstrated a dose dependent increase in thrombomodulin mRNA in response to dbcAMP. Treatment of HUVEC with 20 microM forskolin or 100 microM isobutylmethylxanthine (IBMX) also increased cell-surface thrombomodulin on HUVEC. These agents prevented the interleukin I (IL-I) or tumor necrosis factor (TNF)-induced decrease in thrombomodulin on HUVEC. These data suggest that the expression of thrombomodulin on HUVEC and mouse hemangioma cells may be regulated by intracellular cAMP level.
我们先前报道，人巨核母细胞白血病细胞系MEG-01上血栓调节蛋白的表达可被增加细胞内cAMP的试剂所增强。在本文中，我们研究了这些试剂对培养的人脐静脉内皮细胞（HUVEC）和小鼠血管瘤细胞的作用。用3 mM二丁酰cAMP（dbcAMP）孵育细胞后，HUVEC上功能活性血栓调节蛋白增加约2倍，血管瘤细胞上增加约4倍。这种效应在孵育1小时后即可观察到，并持续至24小时。mRNA的点杂交显示，响应dbcAMP，血栓调节蛋白mRNA呈剂量依赖性增加。用20 μM福司可林或100 μM异丁基甲基黄嘌呤（IBMX）处理HUVEC也可增加其细胞表面血栓调节蛋白。这些试剂可防止白细胞介素I（IL-I）或肿瘤坏死因子（TNF）诱导的HUVEC上血栓调节蛋白的减少。这些数据表明，HUVEC和小鼠血管瘤细胞上血栓调节蛋白的表达可能受细胞内cAMP水平的调节。
