Kelly K A, Hill M R, Youkhana K, Wanker F, Gimble J M
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Infect Immun. 1994 Aug;62(8):3122-8. doi: 10.1128/iai.62.8.3122-3128.1994.
Antioxidants are protective against septic shock in animal models. Recently, free radical scavengers have been found to inhibit the activation of the NF-kappa B protein in a number of cell lines. This transcriptional regulatory protein binds to the promoters of the proinflammatory cytokines tumor necrosis factor, interleukin-6, and the macrophage inflammatory proteins. The current work examined lipopolysaccharide-induced NF-kappa B activation in the J774 macrophage-like cell line and primary peritoneal macrophages from lipopolysaccharide-responsive (C3HeB/Fej) and -nonresponsive (C3H/HeJ) murine strains. The DNA-binding activity of the NF-kappa B protein directly correlated with mRNA expression for the genes encoding the proinflammatory cytokines and the free radical scavenging enzyme, superoxide dismutase. Both the p50 and p65 NF-kappa B subunits were detected on gel supershift assays. Minimal NF-kappa B activity was observed following exposure of C3H/HeJ macrophages to lipopolysaccharide. The antioxidant dimethyl sulfoxide decreased the level of NF-kappa B activation in the J774 cells. This correlated with decreased expression of cytokine mRNAs and tumor necrosis factor bioactivity. These results suggest that modulation of NF-kappa B activation may provide a mechanism through which antioxidants protect against endotoxemia in murine models.
抗氧化剂在动物模型中对脓毒性休克具有保护作用。最近，人们发现自由基清除剂可在多种细胞系中抑制NF-κB蛋白的激活。这种转录调节蛋白可与促炎细胞因子肿瘤坏死因子、白细胞介素-6以及巨噬细胞炎性蛋白的启动子结合。目前的研究检测了脂多糖诱导的J774巨噬细胞样细胞系以及来自脂多糖反应性（C3HeB/Fej）和无反应性（C3H/HeJ）小鼠品系的原代腹腔巨噬细胞中NF-κB的激活情况。NF-κB蛋白的DNA结合活性与编码促炎细胞因子和自由基清除酶超氧化物歧化酶的基因的mRNA表达直接相关。在凝胶超迁移分析中检测到了p50和p65 NF-κB亚基。将C3H/HeJ巨噬细胞暴露于脂多糖后，观察到最小的NF-κB活性。抗氧化剂二甲基亚砜降低了J774细胞中NF-κB的激活水平。这与细胞因子mRNA表达的降低以及肿瘤坏死因子生物活性的降低相关。这些结果表明，调节NF-κB的激活可能提供了一种机制，通过该机制抗氧化剂可在小鼠模型中预防内毒素血症。
