gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells
| Autor: | Qing Jiang, Bruce N. Ames, Ilan Elson-Schwab, Chantal Courtemanche |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Lipopolysaccharides
Metabolite medicine.medical_treatment Nitric Oxide Synthase Type II Inflammation Arachidonic Acids Biology Pharmacology Cell Line chemistry.chemical_compound Isomerism medicine Humans Vitamin E Cyclooxygenase Inhibitors Nitrites Multidisciplinary Macrophages Epithelial Cells Biological Sciences Nitric oxide synthase chemistry Biochemistry Cell culture biology.protein Arachidonic acid Cyclooxygenase medicine.symptom Nitric Oxide Synthase alpha-Tocopherol Reactive Oxygen Species Prostaglandin E Interleukin-1 |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 97(21) |
| ISSN: | 0027-8424 |
| Popis: | Cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E 2 (PGE 2 ) plays a key role in inflammation and its associated diseases, such as cancer and vascular heart disease. Here we report that γ-tocopherol (γT) reduced PGE 2 synthesis in both lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and IL-1β-treated A549 human epithelial cells with an apparent IC 50 of 7.5 and 4 μM, respectively. The major metabolite of dietary γT, 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman (γ-CEHC), also exhibited an inhibitory effect, with an IC 50 of ≈30 μM in these cells. In contrast, α-tocopherol at 50 μM slightly reduced (25%) PGE 2 formation in macrophages, but had no effect in epithelial cells. The inhibitory effects of γT and γ-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. γ-CEHC also inhibited PGE 2 synthesis when exposed for 1 h to COX-2-preinduced cells followed by the addition of arachidonic acid (AA), whereas under similar conditions, γT required an 8- to 24-h incubation period to cause the inhibition. The inhibitory potency of γT and γ-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 γT in lipopolysaccharide-treated macrophages. These findings indicate that γT and its major metabolite possess anti-inflammatory activity and that γT at physiological concentrations may be important in human disease prevention. |
| Databáze: | OpenAIRE |
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