Shimokawa T, Yamamoto K, Yamafuji E, Kojima T, Saito H
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Thromb Haemost. 2001 Aug;86(2):623-9.
Protein S (PS), a co-factor of activated protein C, is a vitamin K-dependent anticoagulant protein and is known to be produced extrahepatically. In the present study, the concentration of PS mRNA was determined tissue by tissue in the mouse, and it was high in lung, adrenal and heart as well as in liver. We further investigated the effects of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 (IL-1) on the PS mRNA expression in murine tissues in vivo. Although LPS and TNF-alpha significantly decreased the expression level of PS mRNA in all tissues examined (e. g., lung, liver, heart, and kidney) and the PS antigen level in plasma, the suppressive effect of IL-1 on PS gene expression was limited to heart. More specifically, considerable amounts of PS mRNA and antigen were expressed in a cultured mouse cardiomyocyte cell line, and again, treatment with IL-1 decreased the PS expression in these cells. These observations raise a possibility that the expression of cardiac PS may contribute to the regional anticoagulant potential in heart, and suggest that the decreased PS expression by cytokines may result in an increase in the systemic and/or regional prothrombotic potential under inflammatory conditions.
蛋白S（PS）是活化蛋白C的一种辅助因子，是一种维生素K依赖的抗凝蛋白，已知在肝外产生。在本研究中，测定了小鼠各组织中PS mRNA的浓度，发现其在肺、肾上腺、心脏以及肝脏中含量较高。我们进一步研究了脂多糖（LPS）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）对小鼠体内组织中PS mRNA表达的影响。尽管LPS和TNF-α显著降低了所有检测组织（如肺、肝、心和肾）中PS mRNA的表达水平以及血浆中PS抗原水平，但IL-1对PS基因表达的抑制作用仅限于心脏。更具体地说，在培养的小鼠心肌细胞系中表达了大量的PS mRNA和抗原，同样，用IL-1处理会降低这些细胞中的PS表达。这些观察结果提示心脏PS的表达可能有助于心脏局部的抗凝潜能，并且表明在炎症条件下细胞因子导致的PS表达降低可能会导致全身和/或局部血栓形成潜能增加。
