Contrasting effects of n-3 and n-6 fatty acids on cyclooxygenase-2 in model systems for arthritis.
Cyclooxygenase-2 (COX-2) is intimately involved in symptoms of arthritis while dietary n-3 polyunsaturated fatty acids (PUFA) are thought to be beneficial. In these experiments, using both bovine and human in vitro systems that mimic features of arthritis, we show that the n-3 PUFA eicosapentaenoic acid (EPA) is able to reduce mRNA and protein levels of COX-2. Activity, as assessed through prostaglandin E(2) formation, was also reduced in a dose-dependent manner. These effects of EPA contrasted noticeably with the n-6 PUFA, arachidonic acid. The data provide direct evidence for a molecular mechanism by which dietary n-3 PUFA, such as EPA, can reduce inflammation and, hence, associated symptoms in arthritis.
Hurst
Samantha
S
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK.
Rees
Sarah G
SG
Randerson
Peter F
PF
Caterson
Bruce
B
Harwood
John L
JL
D000818:Animals; D001168:Arthritis / Q000178:diet therapy* / Q000201:enzymology* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004041:Dietary Fats / Q000494:pharmacology / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans
D052246:Cyclooxygenase 2 Inhibitors; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D051546:Cyclooxygenase 2