de Lima Thais Martins, de Sa Lima Larissa, Scavone Cristoforo, Curi Rui
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof Lineu Prestes, 1524, 05508-900, São Paulo, Brazil.
FEBS Lett. 2006 May 29;580(13):3287-95. doi: 10.1016/j.febslet.2006.04.091. Epub 2006 May 8.
Modulation of macrophage functions by fatty acids (FA) has been studied by several groups, but the effect of FA on nitric oxide production by macrophages has been poorly examined. In the present study the effect of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on NF-kappaB activity and NO production in J774 cells (a murine macrophage cell line) was investigated. All FA tested stimulated NO production at low doses (1-10 microM) and inhibited it at high doses (50-200 microM). An increase of iNOS expression and activity in J774 cells treated with a low concentration of FA (5 microM) was observed. The activity of NF-kappaB was time-dependently enhanced by the FA treatment. The inhibitory effect of FA on NO production may be due to their cytotoxicity, as observed by loss of membrane integrity and/or increase of DNA fragmentation in cells treated for 48 h with high concentrations. The results indicate that, at low concentrations FA increase NO production by J774 cells, whereas at high concentrations they cause cell death.
多个研究小组对脂肪酸（FA）对巨噬细胞功能的调节作用进行了研究，但FA对巨噬细胞一氧化氮产生的影响尚未得到充分研究。在本研究中，研究了棕榈酸、硬脂酸、油酸、亚油酸、花生四烯酸、二十二碳六烯酸和二十碳五烯酸对J774细胞（一种小鼠巨噬细胞系）中NF-κB活性和一氧化氮产生的影响。所有测试的脂肪酸在低剂量（1-10微摩尔）时刺激一氧化氮的产生，而在高剂量（50-200微摩尔）时抑制一氧化氮的产生。观察到用低浓度脂肪酸（5微摩尔）处理的J774细胞中诱导型一氧化氮合酶（iNOS）的表达和活性增加。脂肪酸处理可使NF-κB的活性随时间增强。脂肪酸对一氧化氮产生的抑制作用可能是由于其细胞毒性，在用高浓度脂肪酸处理48小时的细胞中观察到膜完整性丧失和/或DNA片段化增加。结果表明，低浓度的脂肪酸可增加J774细胞一氧化氮的产生，而高浓度时则导致细胞死亡。
