?-Tocopherol and its major metabolite, in contrast to a-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells Ann's NOTE: The ? should be read as gamma. We were unable to upload the correct symbol. Sorry. Qing Jiang, Ilan Elson-Schwab, Chantal Courtemanche, and Bruce N. Ames Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720; and Children's Hospital Oakland Research Institute, 5700 M. L. King Jr. Way, Oakland, CA 94609 Abstract Cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E2 (PGE2 ) plays a key role in inflammation and its associated diseases, such as cancer and vascular heart disease. Here we report that ?-tocopherol (?T) reduced PGE2 synthesis in both lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and IL-1ß-treated A549 human epithelial cells with an apparent IC50 of 7.5 and 4 µM, respectively. The major metabolite of dietary ?T, 2,7,8-trimethyl-2-(ß-carboxyethyl)-6-hydroxychroman (?-CEHC), also exhibited an inhibitory effect, with an IC50 of 30 µM in these cells. In contrast, a-tocopherol at 50 µM slightly reduced (25%) PGE2 formation in macrophages, but had no effect in epithelial cells. The inhibitory effects of ?T and ?-CEHC stemmed from their inhibition of COX-2 activity, rather than affecting protein expression or substrate availability, and appeared to be independent of antioxidant activity. ?-CEHC also inhibited PGE2 synthesis when exposed for 1 h to COX-2-preinduced cells followed by the addition of arachidonic acid (AA), whereas under similar conditions, ?T required an 8- to 24-h incubation period to cause the inhibition. The inhibitory potency of ?T and ?-CEHC was diminished by an increase in AA concentration, suggesting that they might compete with AA at the active site of COX-2. We also observed a moderate reduction of nitrite accumulation and suppression of inducible nitric oxide synthase expression by ?T in lipopolysaccharide-treated macrophages. These findings indicate that ?T and its major metabolite possess anti-inflammatory activity and that ?T at physiological concentrations may be important in human disease prevention. Proc. Natl. Acad. Sci. USA: Vol. 97, No. 21, 1149411499, October 10, 2000 Medical Sciences Copyright © 2000, The National Academy of Sciences Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.