Zhen Qin, Peng-Yuan Wang, Jing-Jing Wan, Yu Zhang, Jie Wei, Yang Sun, Xia Liu
Frontiers in immunology 2020Epidemiological 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. Copyright © 2020 Qin, Wang, Wan, Zhang, Wei, Sun and Liu.
Zhen Qin, Peng-Yuan Wang, Jing-Jing Wan, Yu Zhang, Jie Wei, Yang Sun, Xia Liu. MicroRNA124-IL6R Mediates the Effect of Nicotine in Inflammatory Bowel Disease by Shifting Th1/Th2 Balance Toward Th1. Frontiers in immunology. 2020;11:235
PMID: 32153570
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