Shimokawa T, Yamamoto K, Kojima T, Saito H
First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai, Showa, 466-8550, Nagoya, Japan.
Thromb Res. 2000 Nov 1;100(3):211-21. doi: 10.1016/s0049-3848(00)00332-7.
Tissue factor pathway inhibitor (TFPI) is the protease inhibitor that regulates the extrinsic coagulation pathway initiated by the factor VIIa/TF complex. In this study, we first investigated tissue distribution of TFPI mRNA in the mouse and found that TFPI mRNA expression level was by far the highest in the lung, followed by the heart, adrenal, and adipose tissue. Since little has been known concerning the regulation of TFPI gene expression in vivo, we further analyzed the changes in the TFPI mRNA level in murine tissues after intraperitoneal injection of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1). LPS and TNF-alpha dramatically decreased TFPI mRNA expression in four tissues examined (e.g., lung, heart, kidney, and adipose tissue), whereas the suppressive effect of IL-1 on TFPI mRNA was limited. The down-regulation of TFPI mRNA expression by LPS and TNF-alpha was also observed in cultured mouse endothelial cells and in cardiomyocyte cell lines. The decreased TFPI mRNA expression by LPS and TNF-alpha in tissues and in the specific cell types may contribute to an increase in the local procoagulant potential, resulting in the thrombotic tendency under septic and/or inflammatory conditions.
组织因子途径抑制剂（TFPI）是一种蛋白酶抑制剂，可调节由因子VIIa/TF复合物启动的外源性凝血途径。在本研究中，我们首先调查了TFPI mRNA在小鼠体内的组织分布，发现TFPI mRNA表达水平在肺中最高，其次是心脏、肾上腺和脂肪组织。由于对体内TFPI基因表达的调控了解甚少，我们进一步分析了腹腔注射脂多糖（LPS）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）后小鼠组织中TFPI mRNA水平的变化。LPS和TNF-α显著降低了所检测的四种组织（如肺、心脏、肾脏和脂肪组织）中的TFPI mRNA表达，而IL-1对TFPI mRNA的抑制作用有限。在培养的小鼠内皮细胞和心肌细胞系中也观察到LPS和TNF-α对TFPI mRNA表达的下调。LPS和TNF-α在组织和特定细胞类型中导致的TFPI mRNA表达降低可能有助于局部促凝潜能的增加，从而在脓毒症和/或炎症状态下导致血栓形成倾向。
