Suppression of miR-21 and miR-155 of macrophage by cinnamaldehyde ameliorates ulcerative colitis
Suppression of miR-21 and miR-155 of macrophage by cinnamaldehyde ameliorates ulcerative colitis
复制标题
肉桂醛抑制巨噬细胞的 miR-21 和 miR-155 可改善溃疡性结肠炎
DOI：
10.1016/j.intimp.2018.11.045
复制
发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Yang, Yifu
中科院分区：
文献类型：
--
作者：
Qu, Shulan;Shen, Yunhui;Yang, Yifu
溃疡性结肠炎（UC）是一种主要的炎症性肠病，其发病机制与黏膜免疫功能紊乱有关。肉桂醛（Cinnamaldehyde，CA）是肉桂中的主要活性成分，肉桂是亚洲的传统药用植物，具有良好的上级抗菌、抗炎活性。在这项研究中，我们研究了CA在体内和体外对UC的影响。我们发现，CA减弱DSS诱导的结肠炎的症状，包括体重减轻，疾病活动指数（DAI），结肠长度缩短和炎性细胞浸润。此外，CA降低结肠组织中的促炎细胞因子和NLRP 3炎性体、miR-21和miR-155，此外，基于CA处理组的表面标志物F4/80和IL-10分泌的巨噬细胞百分比降低，表明CA通过激活巨噬细胞来改善UC。在此，CA对巨噬细胞的影响在体外进行了检查。我们发现CA降低了RAW264.7、人巨噬细胞样细胞U937和原代腹腔巨噬细胞活化中促炎细胞因子如TNF-α、IL-1 β、IL-6的水平。此外，在CA处理的LPS刺激的RAW 264. 7细胞中也发现NLRP 3炎性体、miR-21和miR-155的抑制。CA还降低了RAW 264.7中活性氧的产生，AKT、mTOR和COX 2蛋白的磷酸化水平。同时，数据显示，转移的miR-21或miR-155抑制剂抑制IL-1 β和IL-6的水平，而miR-21或miR-155模拟物增加这些表达，CA抑制这些表达。我们的研究结果表明，CA可以通过抑制NLRP 3炎性体激活以及结肠和巨噬细胞中的miR-21和miR-155水平来改善DSS诱导的结肠炎，表明CA可能是治疗UC的潜在有效药物。
Ulcerative colitis (UC) is a major form of inflammatory bowel disease which involved mucosal immune dysfunction. Cinnamaldehyde (CA) is major active compound from cinnamon, a useful traditional medicine in Asia which shows superior antibacterial and anti-inflammatory activity. In this study, we investigated the effects of CA on UC both in vivo and in vitro. We showed that CA attenuated the symptoms of DSS-induced colitis, including loss of body weights, disease activity index (DAI), shortening of the colon lengths and infiltration of inflammatory cells. Moreover, CA decreased the pro-inflammatory cytokines and NLRP3 inflammasome, miR-21 and miR-155 in colon tissues, in addition, the percentage of macrophages was reduced based on the surface marker F4/80 and IL-10 secretion in CA-treated group, suggesting that the CA ameliorate the UC via activation of macrophage. Herein, the effects of CA on macrophage cells were examined in vitro. We found that CA reduced the level of proinflammatory cytokines, such as TNF-alpha, IL-1 beta, IL-6, in the activation of RAW264.7, human macrophage-like cells U937, and primary peritoneal macrophages. Furthermore, the suppression of NLRP3 inflammasome, miR-21 and miR-155 was also found in CA-treated LPS-stimulated RAW264.7 cells. CA also reduced the production of reactive oxygen species, the phosphorylation of AKT, mTOR and COX2 protein level in the RAW264.7. Meanwhile, data revealed that transferred miR-21 or miR-155 inhibitor suppressed levels of IL-1 beta and IL-6, whereas miR-21 or miR-155 mimics increased expressions of these, and CA suppressed these expressions. Our results indicate that CA could ameliorate DSS-induced colitis through inhibition of NLRP3 inflammasome activation and miR-21 and miR-155 levels in colons and macrophage, suggesting that CA might be a potentially effective drug for UC.