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 excessive production in inflammation is thought to be a causative factor for cellular injury and, over the long term, cancer. In the present study, the effects of several fatty acids on NO production in murine macrophage cell line RAW264 cells stimulated with lipopolysaccharide were examined. Suppression of NO production was observed with the omega 3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid, eicosapentaenoic 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 induction of inducible NO synthase gene expression is responsible for the inhibition of NO production by omega 3 PUFAs. The inhibitory effect of omega 3 PUFA on NO production in activated macrophages could contribute to their cancer chemopreventive influence.
Ohata
T
T
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo.
Fukuda
K
K
Takahashi
M
M
Sugimura
T
T
Wakabayashi
K
K
D000818:Animals; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019301:Oleic Acid / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000494:pharmacology
D015525:Fatty Acids, Omega-3; D008041:Linoleic Acids; D008070:Lipopolysaccharides; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D009569:Nitric Oxide; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; D019001:Nitric Oxide Synthase