DIMETHYL-SULFOXIDE MODULATES NF-KAPPA-B AND CYTOKINE ACTIVATION IN LIPOPOLYSACCHARIDE-TREATED MURINE MACROPHAGES
DIMETHYL-SULFOXIDE MODULATES NF-KAPPA-B AND CYTOKINE ACTIVATION IN LIPOPOLYSACCHARIDE-TREATED MURINE MACROPHAGES
复制标题
DOI：
10.1128/iai.62.8.3122-3128.1994
复制
发表时间：
1994-08-01
影响因子：
3.1
通讯作者：
GIMBLE, JM
中科院分区：
文献类型：
--
作者：
KELLY, KA;HILL, MR;GIMBLE, JM
抗氧化剂在动物模型中对感染性休克具有保护作用。最近，自由基清除剂已被发现在许多细胞系中抑制NF-κ B蛋白的活化。该转录调节蛋白结合促炎细胞因子肿瘤坏死因子、白细胞介素-6和巨噬细胞炎性蛋白的启动子。目前的工作研究了脂多糖诱导的NF-κ B B激活的J774巨噬细胞样细胞系和主要的腹腔巨噬细胞从脂多糖响应（C3 He B/Fej）和非响应（C3 H/HeJ）的小鼠品系。NF-κ B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。p50和p65 NF-κ B亚基均在凝胶超移试验中检测到。C3 H/HeJ巨噬细胞暴露于脂多糖后，观察到最小的NF-κ B活性。抗氧化剂二甲基亚砜降低了J774细胞中NF-κ B的活化水平。这与细胞因子mRNA表达和肿瘤坏死因子生物活性降低相关。这些结果表明，NF-κ B活化的调节可能提供了一种机制，通过这种机制，抗氧化剂在小鼠模型中保护免受内毒素血症。
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.