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 E2 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.

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Fig. 5



Arachidonic acid


5-bromo-4-chlorindolyl phosphate




All cis-Δ4, 7, 10, 13, 16, 19-docosahexaenoic acid


Dulbecco’s modified Eagle’s medium


All cis-Δ5, 8, 11, 14, 17-eicosapentaenoic acid


Foetal calf serum


Fibroblast growth factor


Glyceraldehyde-3-phosphate dehydrogenase




Nitroblue tetrazolium


Non-steroidal anti-inflammatory drugs




Platelet-derived growth factor




Polyunsaturated fatty acid


Rheumatoid arthritis


Tumour necrosis factor-α


TRIZMA saline azide


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This investigation was supported financially by the Arthritis Research Campaign and the Biotechnology and Biological Sciences Research Council (Grant D16961) for which we are grateful.

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Correspondence to John L. Harwood.

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Hurst, S., Rees, S.G., Randerson, P.F. et al. Contrasting Effects of n-3 and n-6 Fatty Acids on Cyclooxygenase-2 in Model Systems for Arthritis. Lipids 44, 889 (2009).

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  • Cyclooxygenase-2 (COX-2) expression
  • COX-2 activity
  • Arthritis
  • n-3 Polyunsaturated fatty acids