Ohdama S, Takano S, Ohashi K, Miyake S, Aoki N
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Thromb Res. 1991 Jun 15;62(6):745-55. doi: 10.1016/0049-3848(91)90378-a.
Thrombomodulin (TM) expression has been reported to be down-regulated by cytokines (endotoxin, interleukin-1, and tumor necrosis factor). We report, in the present study, up-regulation of surface TM antigen of human umbilical vein endothelial cells (HUVECs) by pentoxifylline (PTX) which is one of the agents that can increase intracellular cyclic AMP in HUVECs at therapeutic concentrations. Surface TM antigen was measured by an enzyme immunoassay. PTX increased surface TM antigen and intracellular cAMP in HUVECs in a dose dependent manner. Upregulation of TM by PTX was due to de novo synthesis of TM protein resulting from increased TM mRNA levels. PTX counterbalanced the TNF-induced suppression of TM expression. These results suggest that protein kinase A may be involved in cellular regulatory mechanism for TM expression and PTX may protect partially against TNF-induced endothelial cell injury and restore anticoagulant state of endothelium.
据报道，血栓调节蛋白（TM）的表达会被细胞因子（内毒素、白细胞介素-1和肿瘤坏死因子）下调。在本研究中，我们报告了己酮可可碱（PTX）可上调人脐静脉内皮细胞（HUVECs）表面的TM抗原，PTX是一种在治疗浓度下可增加HUVECs细胞内环磷酸腺苷（cAMP）的药物。通过酶免疫测定法测量表面TM抗原。PTX以剂量依赖的方式增加HUVECs表面的TM抗原和细胞内cAMP。PTX对TM的上调是由于TM mRNA水平增加导致TM蛋白的从头合成。PTX抵消了肿瘤坏死因子（TNF）诱导的TM表达抑制。这些结果表明蛋白激酶A可能参与了TM表达的细胞调节机制，并且PTX可能部分保护内皮细胞免受TNF诱导的损伤，并恢复内皮的抗凝状态。
