Wu D, Mura C, Beharka A A, Han S N, Paulson K E, Hwang D, Meydani S N
Nutritional Immunology Laboratory, Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
Am J Physiol. 1998 Sep;275(3):C661-8. doi: 10.1152/ajpcell.1998.275.3.C661.
We previously showed that increased macrophage and PGE2 production with age is due to enhanced cyclooxygenase (COX) activity and COX-2 expression. This study determined the effect of vitamin E supplementation on macrophage PGE2 synthesis in young and old mice and its underlying mechanism. Mice were fed 30 or 500 parts per million vitamin E for 30 days. Lipopolysaccharide (LPS)-stimulated macrophages from old mice produced significantly more PGE2 than those from young mice. Vitamin E supplementation reversed the increased PGE2 production in old mice but had no effect on macrophage PGE2 production in young mice. In both LPS-stimulated and unstimulated macrophages, COX activity was significantly higher in old than in young mice at all intervals. Vitamin E supplementation completely reversed the increased COX activity in old mice to levels comparable to those of young mice but had no effect on macrophage COX activity of young mice or on COX-1 and COX-2 protein or COX-2 mRNA expression in young or old mice. Thus vitamin E reverses the age-associated increase in macrophage PGE2 production and COX activity. Vitamin E exerts its effect posttranslationally, by inhibiting COX activity.
我们之前的研究表明，随着年龄增长，巨噬细胞和前列腺素E2（PGE2）产量增加是由于环氧化酶（COX）活性增强以及COX-2表达增加所致。本研究确定了补充维生素E对年轻和老年小鼠巨噬细胞PGE2合成的影响及其潜在机制。给小鼠喂食百万分之30或500的维生素E，持续30天。来自老年小鼠的脂多糖（LPS）刺激的巨噬细胞产生的PGE2明显多于来自年轻小鼠的巨噬细胞。补充维生素E可逆转老年小鼠中PGE2产量的增加，但对年轻小鼠巨噬细胞的PGE2产量没有影响。在LPS刺激和未刺激的巨噬细胞中，在所有时间间隔内，老年小鼠的COX活性均显著高于年轻小鼠。补充维生素E可将老年小鼠增加的COX活性完全逆转至与年轻小鼠相当的水平，但对年轻小鼠巨噬细胞的COX活性或对年轻或老年小鼠的COX-1和COX-2蛋白或COX-2 mRNA表达没有影响。因此，维生素E可逆转与年龄相关的巨噬细胞PGE2产量和COX活性增加。维生素E通过抑制COX活性在翻译后发挥作用。
