Clostridium difficile cytotoxin inhibits protein synthesis in fibroblasts and intestinal mucosa.
Clostridium difficile cytotoxin inhibits protein synthesis in fibroblasts and intestinal mucosa.
复制标题
艰难梭菌细胞毒素抑制成纤维细胞和肠粘膜的蛋白质合成。
DOI：
10.1016/s0016-5085(86)80010-5
复制
发表时间：
1986
期刊：
影响因子：
29.4
通讯作者：
LaMont,JT
中科院分区：
文献类型：
--
作者：
Pothoulakis,C;Triadafilopoulos,G;Clark,M;Franzblau,C;LaMont,JT
艰难梭菌结肠炎的病理生理学被认为是通过释放毒素A（一种肠毒素）和毒素B（一种细胞毒素）介导的。我们比较了毒素B对IMR-90成纤维细胞和器官培养中仓鼠食管、胃、胆囊、小肠和盲肠中蛋白质合成的不同影响。低浓度的毒素B刺激（p < 0.001）[3 H]亮氨酸掺入成纤维细胞蛋白，而在较高剂量时，它抑制掺入（p < 0.001）。这种双相效应与细胞变圆无关，也不是由前体摄取的变化引起的。纯化的毒素B对无细胞兔网织红细胞翻译系统中的蛋白质合成没有影响，表明完整成纤维细胞单层和肠外植体中蛋白质合成的抑制是毒素B对某些其他细胞靶点的影响的结果。毒素B以剂量依赖性方式显著抑制仓鼠盲肠外植体中的蛋白质合成。同样，这种抑制不是由改变前体摄取介导的。毒素B显着抑制仓鼠末端回肠、盲肠和乙状结肠的体外蛋白质合成，但不抑制食道、胆囊、胃或十二指肠的蛋白质合成。这些结果表明，毒素B介导的蛋白质合成抑制可能是组织培养细胞和肠上皮细胞的普遍毒性作用。远端肠上皮蛋白质合成的抑制可能有助于由该微生物引起的结肠炎的病理生理学。
The pathophysiology ofClostridium difficilecolitis is thought to be mediated by release of toxin A, an enterotoxin, and toxin B, a cytotoxin. We compared the differential effects of toxin B on protein synthesis in IMR-90 fibroblasts and in hamster esophagus, stomach, gallbladder, small intestine, and cecum in organ culture. Toxin B in low concentrations stimulated (p < 0.001) incorporation of [3H]leucine into fibroblast proteins, whereas at higher dosages it inhibited incorporation (p < 0.001). This biphasic effect was independent of cell rounding and was not caused by a change in uptake of precursor. Purified toxin B had no effect on protein synthesis in a cell-free rabbit reticulocyte translation system, indicating that inhibition of protein synthesis in intact fibroblast monolayers and intestinal explants is a consequence of toxin B effect on some other cellular target. Toxin B significantly inhibited protein synthesis in hamster cecal explants in a dose-dependent fashion. Again, this inhibition was not mediated by altered precursor uptake. Toxin B significantly inhibited in vitro protein synthesis in hamster terminal ileum, cecum, and sigmoid colon, but not in esophagus, gallbladder, stomach, or duodenum. These results suggest that toxin B-mediated inhibition of protein synthesis may be a generalized toxic effect in tissue culture cells and intestinal epithelium. Inhibition of protein synthesis in the distal intestinal epithelium may contribute to the pathophysiology of colitis caused by this organism.