期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 18, 期 4, 页码 250-258出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2006.04.003
关键词
macrophage; eicosapentaenoic acid; docosahexaenoic acid; cytokines; nuclear factor kappa B
A number of studies have investigated the effects of fish oil on the production of pro-inflammatory cytokines using peripheral blood mononuclear cell models. The majority of these studies have employed heterogeneous blends of long-chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexacnoic acid (DHA), which preclude examination of the individual effects of LC n-3 PUFA. This study investigated the differential effects of pure EPA and DHA on cytokine expression and nuclear factor kappa B (NF-kappa B) activation in human THP-1 monocyte-derived macrophages. Pretreatment with 100 mu M EPA and DHA significantly decreased lipopolysaccharide (LPS)-stimulated THP-1 macrophage tumor necrosis factor (TNF) alpha, interleukin (IL) 1 beta and IL-6 production (P <.02), compared to control cells. Both EPA and DHA reduced TNF-alpha, IL-1 beta and IL-6 mRNA expression. In all cases, the effect of DHA was significantly more potent than that of EPA (P <.01). Furthermore, a low dose (25 mu M) of DHA had a greater inhibitory effect than that of EPA on macrophage IL-1 beta (P <.01 and P <.04, respectively) and IL-6 (P <.003 and P <.003, respectively) production following 0.01 and 0.1 mu g/ml LPS stimulation. Both EPA and DHA down-regulated LPS-induced NF-kappa B/DNA binding in THP-1 macrophages by similar to 13% (P <=.03). DHA significantly decreased macrophage nuclear p65 expression (P <=.05) and increased cytoplasmic I kappa B alpha expression (P <=.05). Although similar trends were observed with EPA, they were not significant. Our findings suggest that DHA may be more effective than EPA in alleviating LPS-induced pro-inflammatory cytokine production in macrophages - an effect that may be partly mediated by NF-kappa B. Further work is required to elucidate additional divergent mechanisms to account for apparent differences between EPA and DHA. (c) 2007 Elsevier Inc. All rights reserved.
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