Robinson D R, Urakaze M, Huang R, Taki H, Sugiyama E, Knoell C T, Xu L, Yeh E T, Auron P E
Arthritis Unit of the Medical Services, Massachusetts General Hospital, Boston 02114, USA.
Lipids. 1996 Mar;31 Suppl:S23-31. doi: 10.1007/BF02637046.
n-3 Polyunsaturated fatty acids abundant in marine lipids suppress certain inflammatory and immune reactions, and dietary marine lipid supplements have antiinflammatory effects in experimental and human autoimmune disease. Previous work by other investigators demonstrated that dietary marine lipid supplements suppressed production of cytokines from stimulated human peripheral blood mononuclear cells ex vivo. The present study further documents the ability of n-3 fatty acids to inhibit cytokine formation, and in part defines the mechanism of the inhibition of production of interleukin-1 beta (IL-1 beta) by dietary n-3 fatty acid. Female BALB/c mice were each fed a fat-free balanced diet to which was added either a refined fish oil (FO) preparation as a source of n-3 fatty acid, or beef tallow (BT), which consisted primarily of saturated and monoenoic fatty acids. After ingesting the experimental diets for periods ranging from 3 to 12 wk. spleen cell preparations were stimulated ex vivo with either lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA), and proIL-1 beta mRNA (IL-1 beta mRNA) was measured by northern analysis. Levels of IL-1 beta mRNA in both LPS- and PMA-stimulated cells from BT-fed mice were elevated to a greater extent than in cells from FO-fed mice, at most concentrations of LPS and PMA. Stability of LPS-stimulated mRNA levels after actinomycin D was similar for BT and FO groups, indicating that lower levels of IL-1 mRNA with FO groups was related to suppressed IL-1 gene transcription and not due to accelerated transcript degradation. Nuclear run-on transcription assays revealed a more transient expression of the IL-1 beta gene in LPS-stimulated spleen cells from FO-fed mice compared to cells from BT-fed mice. We conclude that dietary marine lipids reduce transient expression of the IL-1 beta gene in stimulated splenic monocytic cells. Preliminary results from nuclear run-on transcription assays indicate that n-3 fatty acids may not change the initial rate of gene transcription but may promote more rapid shutting down of transcription of this gene after induction than do alternative lipids.
海洋脂质中富含的n-3多不饱和脂肪酸可抑制某些炎症和免疫反应，膳食海洋脂质补充剂在实验性和人类自身免疫性疾病中具有抗炎作用。其他研究人员之前的工作表明，膳食海洋脂质补充剂可在体外抑制受刺激的人外周血单核细胞产生细胞因子。本研究进一步证明了n-3脂肪酸抑制细胞因子形成的能力，并部分确定了膳食n-3脂肪酸抑制白细胞介素-1β（IL-1β）产生的机制。给雌性BALB/c小鼠喂食无脂平衡饮食，其中添加精制鱼油（FO）制剂作为n-3脂肪酸的来源，或添加主要由饱和脂肪酸和单不饱和脂肪酸组成的牛脂（BT）。在摄入实验性饮食3至12周后，用脂多糖（LPS）或佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）体外刺激脾细胞制备物，并通过Northern分析测量前IL-1β mRNA（IL-1β mRNA）。在大多数LPS和PMA浓度下，BT喂养小鼠的LPS和PMA刺激细胞中的IL-1β mRNA水平比FO喂养小鼠的细胞升高幅度更大。放线菌素D处理后，LPS刺激的mRNA水平稳定性在BT组和FO组相似，表明FO组较低的IL-1 mRNA水平与IL-1基因转录受抑制有关，而非转录本降解加速。核转录分析显示，与BT喂养小鼠的细胞相比，FO喂养小鼠的LPS刺激脾细胞中IL-1β基因的表达更短暂。我们得出结论，膳食海洋脂质可降低刺激的脾单核细胞中IL-1β基因的短暂表达。核转录分析的初步结果表明，n-3脂肪酸可能不会改变基因转录的初始速率，但与其他脂质相比，可能在诱导后促进该基因转录更快地关闭。
