SUPPRESSION OF NITRIC-OXIDE PRODUCTION IN LIPOPOLYSACCHARIDE-STIMULATED MACROPHAGE CELLS BY OMEGA-3 POLYUNSATURATED FATTY-ACIDS

Although nitric oxide (NO) is an important biological mediator, its ex cessive production in inflammation is thought to be a causative factor for cellular injury and, over the long term, cancer. In the present s tudy, the effects of several fatty acids on NO production in murine ma crophage cell line RAW264 cells stimulated with lipopolysaccharide wer e examined. Suppression of NO production was observed with the omega 3 polyunsatarated fatty acids (PUFAs), docosahexaenoic acid, eicosapent aenoic acid and alpha-linolenic acid, in a dose-dependent fashion. In contrast, no inhibition was observed with omega 6 PUFA (linoleic acid) , omega 9 PUFA (oleic acid) or a saturated fatty acid (stearic acid). Western and northern blot analyses suggested that suppression of the i nduction of inducible NO synthase gene expression is responsible for t he inhibition of NO production by omega 3 PUFAs. The inhibitory Effect of omega 3 PUFA on NO production in activated macrophages could contr ibute to their cancer chemopreventive influence.