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目的哺乳动物新生期肠上皮高表达mi R-146a介导固有免疫耐受,本研究探讨mi R-146a下降后肠上皮继续保持耐受状态的分子机制。方法定量PCR分析肠上皮mi R-146a与mi R-155表达模式,体外实验比较二者激活的刺激强度差异;转染及免疫印迹实验分析mi R-155在肠上皮免疫耐受中的功能及其可能调控靶标;小鼠提前断奶实验分析影响mi R-155激活的关键因素。结果肠上皮mi R-146a在新生期高表达并在断奶期降至极低水平,mi R-155则在断奶期剧烈上调;肠上皮中mi R-155激活强度显著高于mi R-146a;肠上皮高表达的mi R-155通过靶向抑制TAB2、IKKε、NIK等抑制炎症应答而非促进炎症;肠上皮mi R-155激活表达与哺乳动物断奶时间相关。结论哺乳动物肠道发育中,mi R-146a与mi R-155在断奶期发生功能接力,依次在新生期和成年期介导肠上皮固有免疫耐受。
Purpose Mammalian neonatal intestinal epithelium overexpression mi R-146a mediates innate immune tolerance. This study was aimed to investigate the molecular mechanism of the continued survival of the intestinal epithelium following mi R-146a decline. Methods Quantitative PCR was used to analyze the expressions of mi R-146a and mi R-155 in intestinal epithelium. The differences in the intensity of stimulation between the two groups were compared in vitro. The function of mi R-155 in immune tolerance of intestinal epithelium was analyzed by transfection and western blotting. It may regulate the target; early mouse weaning assay analyzes the key factors that influence the activation of mi R-155. Results The mi R-146a in the intestinal epithelium was highly expressed during the neonatal period and reached a very low level during weaning. Mi R-155 was dramatically up-regulated during weaning; the mi R-155 activation in the intestinal epithelium was significantly higher than that of mi R-146a; MiR-155, which is highly expressed in the gut epithelium, inhibits inflammatory responses by targeting inhibition of TAB2, IKKε, NIK, and the like but not promotes inflammation; activation of intestinal epithelial mi R-155 is associated with mammalian weaning time. Conclusion mi R-146a and mi R-155 are functional relay during weaning in mammalian gut development, which in turn mediates the inherent immunological tolerance of intestinal epithelium in the newborn and adulthood.