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Am J Physiol Cell Physiol 275: C661-C668, 1998;
0363-6143/98 $5.00
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Vol. 275, Issue 3, C661-C668, September 1998

Age-associated increase in PGE2 synthesis and COX activity in murine macrophages is reversed by vitamin E

Dayong Wu1, Casilda Mura1, Alison A. Beharka1, Sung Nim Han1, K. Eric Paulson2,3, Daniel Hwang4, and Simin Nikbin Meydani1,5

1 Nutritional Immunology Laboratory and 2 Genetics Laboratory, Jean Mayer Human Nutrition Research Center on Aging at Tufts University, 5 Department of Pathology, Sackler Graduate School of Biomedical Sciences, and 3 Departments of Biochemistry and Physiology, Tufts University, Boston, Massachusetts 02111; and 4 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808

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.

cyclooxygenase; immune function; prostaglandins; aging


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