Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3
Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3
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尼古丁通过调节 microRNA-124 和 STAT3 预防 DSS 结肠炎
DOI：
10.1007/s00109-016-1473-5
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发表时间：
2017-02-01
影响因子：
4.7
通讯作者：
Liu, Xia
中科院分区：
文献类型：
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作者：
Qin, Zhen;Wan, Jing-Jing;Liu, Xia
尽管人们普遍认为尼古丁是吸烟对溃疡性结肠炎的有益影响的原因，但其潜在的机制仍不清楚。我们先前的发现尼古丁通过诱导miR-124抑制炎症反应，这促使我们询问miRNA是否参与尼古丁对UC的保护作用。我们目前的研究发现，miR-124在UC患者和DSS结肠炎小鼠的结肠组织中表达上调。尼古丁治疗进一步增强了从人类溃疡性结肠粘膜和DSS小鼠溃疡性结肠组织分离的淋巴细胞中miR-124在浸润性淋巴细胞和上皮细胞中的表达。此外，miR-124基因的敲除显著减弱了尼古丁对小鼠结肠炎和IL-6处理的Caco-2结肠上皮细胞的有利作用。进一步的分析表明，尼古丁在体内和IL-6处理的Caco-2细胞和Jurkat人T淋巴细胞中抑制STAT3的激活，其中miR-124基因敲除导致STAT3的激活增加。单独阻断STAT3活性对DSS结肠炎有利，同时也取消尼古丁在该模型中的保护作用。这些数据表明尼古丁通过诱导miR-124和抑制STAT3在UC中发挥保护作用，提示miR-124/STAT3系统是UC治疗干预的潜在靶点。尼古丁上调溃疡性结肠组织和细胞miR-124的表达。尼古丁对DSS结肠炎小鼠和上皮细胞的保护作用需要miR-124。尼古丁对DSS结肠炎的保护作用依赖于阻断STAT3的激活。miR-124介导尼古丁对STAT3/p-STAT3的抑制作用。
Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis, the underlying mechanisms remain not well understood. Our previous finding that nicotine inhibits inflammatory responses through inducing miR-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine against UC. Our present study found that miR-124 expression is upregulated in colon tissues from UC patients and DSS colitis mice. Nicotine treatment further augmented miR-124 expression in lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells. Moreover, knockdown of miR-124 significantly diminished the beneficial effect of nicotine on murine colitis and IL-6-treated Caco-2 colon epithelial cells. Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6 treated Caco-2 cells and Jurkat human T lymphocytes, in which miR-124 knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine's protective effect in this model. These data indicate that nicotine exerts its protective action in UC through inducing miR-124 and inhibiting STAT3, and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.Nicotine upregulates miR-124 expression in ulcerative colon tissues and cells.MiR-124 is required for the protective role of nicotine in DSS colitis mice and epithelial cells.The protective effect of nicotine in murine DSS colitis depends on blocking STAT3 activation.MiR-124 mediates the inhibitory role of nicotine on STAT3/p-STAT3.Targeting miR-124 and STAT3 represents a novel approach for treating ulcerative colitis.