Epidemiological investigations have shown that smoking ameliorates ulcerative colitis (UC) but exacerbates Crohn's disease (CD), diseases that feature a Th2-mediated and Th1-mediated response, respectively. Cigarette extracts, especially nicotine, affect the Th1/Th2 balance. We previously reported that nicotine protects against mouse DSS colitis (similar to UC) by enhancing microRNA-124 (miR-124) expression. Intriguingly, elevation of miR-124 in CD is reported to aggravate the disease. Here we investigate the dual regulation of miR-124 in inflammatory bowel diseases (IBDs), which may explain the similar bidirectional regulation of tobacco. We found that overexpressed miR-124 protected against mouse DSS-induced colitis with a Th1 polarization in peripheral blood lymphocytes and colon tissues, which was also found in human peripheral blood lymphocytes. Conversely, miR-124 knockdown worsened DSS murine colitis with a Th2 polarization. Moreover, knockdown of miR-124 could eliminate the polarization toward Th1 after nicotine treatment, suggesting that miR-124 mediates the effect of nicotine on the Th1/Th2 balance. In addition, interference of IL-6R, which is a downstream target of miR-124, could remarkably weaken the Th1 polarization induced by miR-124. Taken together, these results suggest that nicotine shifts the balance of Th1/Th2 toward Th1 via a miR-124-mediated IL-6R pathway, which might explain its dual role in IBDs.

流行病学研究表明，吸烟可改善溃疡性结肠炎（UC），但会加剧克罗恩氏病（CD），克罗恩氏病（CD）分别具有Th2介导的反应和Th1介导的反应。香烟提取物，尤其是尼古丁，会影响Th1 / Th2平衡。我们先前曾报道尼古丁可通过增强microRNA-124（miR-124）表达来预防小鼠DSS结肠炎（类似于UC）。有趣的是，据报道CD中miR-124升高会加重疾病。在这里，我们研究了炎症性肠病（IBDs）中miR-124的双重调控，这可能解释了烟草的类似双向调控。我们发现，过度表达的miR-124可抵抗小鼠DSS诱导的结肠炎，并在外周血淋巴细胞和结肠组织中发生Th1极化，在人类外周血淋巴细胞中也发现了这种现象。相反，miR-124敲低会使具有Th2极化的DSS鼠结肠炎恶化。此外，敲低miR-124可以消除尼古丁处理后朝向Th1的极化，表明miR-124介导了尼古丁对Th1 / Th2平衡的影响。此外，作为miR-124下游靶标的IL-6R的干扰可显着减弱miR-124诱导的Th1极化。两者合计，这些结果表明尼古丁通过miR-124介导的IL-6R途径使Th1 / Th2的平衡向Th1转移，这可能解释了其在IBD中的双重作用。提示miR-124介导了尼古丁对Th1 / Th2平衡的影响。此外，作为miR-124下游靶标的IL-6R的干扰可显着减弱miR-124诱导的Th1极化。两者合计，这些结果表明尼古丁通过miR-124介导的IL-6R途径使Th1 / Th2的平衡向Th1转移，这可能解释了其在IBD中的双重作用。提示miR-124介导了尼古丁对Th1 / Th2平衡的影响。此外，作为miR-124下游靶标的IL-6R的干扰可显着减弱miR-124诱导的Th1极化。两者合计，这些结果表明尼古丁通过miR-124介导的IL-6R途径使Th1 / Th2的平衡向Th1转移，这可能解释了其在IBD中的双重作用。