Bhattacharya Arunabh, Chandrasekar Bysani, Rahman Md Mizanur, Banu Jameela, Kang Jing X, Fernandes Gabriel
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Biochem Biophys Res Commun. 2006 Oct 27;349(3):925-30. doi: 10.1016/j.bbrc.2006.08.093. Epub 2006 Aug 24.
Both n-3 fatty acids (n-3 FA) and calorie-restriction (CR) exert anti-inflammatory effects in animal models of autoimmunity and inflammation. In the present study we investigated the synergistic anti-inflammatory effects of n-3 FA and CR on LPS-mediated inflammatory responses using fat-1 transgenic mice that generate n-3 FA endogenously. Wild-type (WT) and fat-1 mice were maintained on ad libitum (AL) or CR (40% less than AL) diet for 5 mo; splenocytes were cultured in vitro with/without LPS. Our results show: (i) no difference in body weights between WT and fat-1 mice on AL or CR diets, (ii) lower n-6/n-3 FA ratio in splenocytes from fat-1 mice on both AL and CR diets, (iii) significant reduction in NF-kappaB (p65/p50) and AP-1 (c-Fos/c-Jun) DNA-binding activities in splenocytes from fat-1/CR mice following LPS treatment, and (iv) significant reduction in kappaB- and AP-1-responsive IL-6 and TNF-alpha secretion following LPS treatment in splenocytes from fat-1/CR mice. The inhibition of LPS-mediated effects was more pronounced in fat-1/CR mice when compared to fat-1/AL or WT/CR mice. These data show that transgenic expression of fat-1 results in decreased pro-inflammatory n-6 FA, and demonstrate for the first time that splenocytes from fat-1 mice on CR diet exhibit reduced pro-inflammatory response when challenged with LPS. These results suggest that n-3 lipids with moderate CR may confer protection in autoimmune and inflammatory diseases.
n-3脂肪酸（n-3 FA）和热量限制（CR）在自身免疫和炎症的动物模型中均具有抗炎作用。在本研究中，我们使用可内源性生成n-3 FA的fat-1转基因小鼠，研究了n-3 FA和CR对脂多糖（LPS）介导的炎症反应的协同抗炎作用。将野生型（WT）和fat-1小鼠随意进食（AL）或热量限制（比AL少40%）饮食5个月；脾细胞在体外用/不用LPS进行培养。我们的结果显示：（i）在AL或CR饮食条件下，WT和fat-1小鼠的体重没有差异；（ii）在AL和CR饮食条件下，fat-1小鼠脾细胞中的n-6/n-3 FA比值较低；（iii）LPS处理后，fat-1/CR小鼠脾细胞中NF-κB（p65/p50）和AP-1（c-Fos/c-Jun）的DNA结合活性显著降低；（iv）LPS处理后，fat-1/CR小鼠脾细胞中κB和AP-1反应性白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的分泌显著减少。与fat-1/AL或WT/CR小鼠相比，fat-1/CR小鼠对LPS介导的效应的抑制作用更明显。这些数据表明，fat-1的转基因表达导致促炎n-6 FA减少，并首次证明，CR饮食条件下的fat-1小鼠脾细胞在受到LPS刺激时表现出较低的促炎反应。这些结果表明，适量CR的n-3脂质可能对自身免疫和炎症性疾病具有保护作用。
